Systems and methods of ablating cardiac tissue

ABSTRACT

The subject of this disclosure includes systems, devices and methods to treat a predetermined patient population for paroxysmal atrial fibrillation, the method including ablating tissue of one or more targeted pulmonary veins with one or more of a plurality of the electrodes of an independently controlled multi-electrode radiofrequency balloon catheter, the balloon catheter comprising the plurality of electrodes for radiofrequency ablation that are independently controllable; determining a predictor, based on ablation parameters of the balloon catheter, of single shot pulmonary vein isolation (PVI) success rate; and achieving, based on the predictor and step of ablating tissue, a single shot isolation PVI success rate in the isolation of all targeted pulmonary veins for the predetermined patient population.

PRIORITY AND CROSS-REFERENCE TO RELATED APPLICATIONS

This application claims priority under 35 USC 119 and 365 (as well asthe Paris Convention) to U.S. provisional patent application No.62/731,525 filed Sep. 14, 2018, U.S. provisional patent application No.62/754,275 filed Nov. 1, 2018, U.S. provisional patent application No.62/771,896 filed Nov. 27, 2018, U.S. provisional patent application No.62/886,729 filed Aug. 14, 2019, and to U.S. provisional patentapplication No. 62/889,471 filed Aug. 20, 2019 and to U.S. provisionalpatent application No. 62/873,636 filed Jul. 12, 2019. The contents ofthese United States provisional patent applications are incorporatedherein by reference in their entirety as if set forth verbatim.

FIELD

This disclosure relates to medical devices designed to treat cardiacarrhythmia.

BACKGROUND

Cardiac arrhythmias, such as atrial fibrillation (AF), occur whenregions of cardiac tissue abnormally conduct electric signals toadjacent tissue. This disrupts the normal cardiac cycle and causesasynchronous rhythm. Certain procedures exist to treat arrhythmia,including surgically disrupting the origin of the signals causing thearrhythmia and disrupting the conducting pathway for such signals. Byselectively ablating cardiac tissue by application of energy via acatheter, it is sometimes possible to cease or modify the propagation ofunwanted electrical signals from one portion of the heart to another.The ablation process destroys the unwanted electrical pathways byformation of non-conducting lesions.

With this in mind, it is understood that AF is the most common sustainedarrhythmia in humans. It affects anywhere from 0.4% to 1% of the generalpopulation and increases in prevalence with age to approximately 10% inpatients over 80 years of age. The primary clinical benefit of AFablation is improvement in quality of life resulting from theelimination of arrhythmia-related symptoms such as palpitations,fatigue, or effort intolerance.

However, due to variances in human anatomy, ostia and tubular regions inthe heart come in all sizes. Thus, conventional balloon or inflatablecatheters may not have necessary flexibility to accommodate differentshapes and sizes while having sufficient structural support foreffective circumferential contact with tissue. In particular, ablationelectrodes that provide greater surface contact may lack sufficientflexibility. Moreover, delicate wires such as those of electrode leadwires and/or thermocouple wires and their solder joints need support andprotection from breakage and damage during both assembly and use in thepatient's body. Additionally, because the balloon configuration isradially symmetrical and multiple electrode elements surround theballoon configuration, determining the orientation of the balloonelectrode assembly under fluoroscopy has also posed challenges.

SUMMARY

Accordingly, the inventors of this disclosure have recognized that thereis a need for a balloon or a catheter having an inflatable member withcontact electrodes that can contact more tissue area while remainingsufficiently flexible to accommodate different anatomy and the tighterspace constraints of an ostium and a pulmonary vein. The inventors haverecognized a need for a balloon catheter to carry an electrode assemblywith adaptations for the ostium and pulmonary vein that can bemanufactured from a generic flexible circuit. There is a further desirefor a balloon catheter capable of multiple functions includingdiagnostic and therapeutic functions, such as ablation, pacing,navigation, temperature sensing, electropotential sensing and impedancesensing, and be adaptive for use with other catheters, including a lassocatheter or a focal catheter.

The solution of this disclosure resolves these and other issues of theart.

The subject of this disclosure is the use of a multi-electrode RFballoon catheter and a multi-electrode diagnostic catheter for thetreatment of paroxysmal and/or drug refractory atrial fibrillation toachieve at least one of a predetermined clinical effectiveness and acuteeffectiveness for a predetermined population size. The inventors believethat there are theoretical advantages of a multi-electrode RF ballooncatheter in conjunction with the multi-electrode diagnostic catheter ofthis disclosure, which includes high probability of single-shotpulmonary vein isolation with minimal collateral damage to non-pulmonaryvein structures, but without the drawbacks of excessive heating orcooling of the surrounding tissue. In some examples, a multi-electrodeRF balloon of the multi-electrode RF balloon catheter is configured todeliver directionally-tailored energy using multiple electrodes,optimizing safety and/or efficacy. In particular, examples of thisdisclosure are suited for isolation of the atrial pulmonary veins intreatment of subjects with paroxysmal atrial fibrillation.

In some examples, a method or use is disclosed to treat a predeterminedpatient population for paroxysmal atrial fibrillation. The method or usecan include ablating tissue of one or more targeted pulmonary veins withone or more of a plurality of the electrodes of an independentlycontrolled multi-electrode radiofrequency balloon catheter, the ballooncatheter comprising the plurality of electrodes for radiofrequencyablation that are independently controllable; determining acharacteristic, based on ablation parameters of the balloon catheter, ofsingle shot pulmonary vein isolation (PVI) success rate; and achieving,based on the characteristic and step of ablating tissue, a single shotisolation PVI success rate in the isolation of all targeted pulmonaryveins for the predetermined patient population.

In some examples, the step of achieving the single shot isolation PVIsuccess rate includes further ablating tissue of one or more targetedpulmonary veins, based on the characteristic, with one or more of aplurality of the electrodes.

In some examples, the step of achieving the single shot isolation PVIsuccess rate includes ceasing further tissue ablation with themulti-electrode radiofrequency balloon catheter, based on thecharacteristic.

In some examples, the step of achieving the single shot isolation PVIsuccess rate includes achieving at least about a 91.7% success rate byablating with a pre-ablation mean initial impedance of less than about95Ω.

In some examples, the step of achieving the single shot isolation PVIsuccess rate includes achieving at least about a 91.7% success rate byablating with a pre-ablation highest initial impedance of less thanabout 100Ω.

In some examples, the step of achieving the single shot isolation PVIsuccess rate includes achieving at least about 87% success rate byablating with a pre-ablation initial anterior wall impedance of lessthan about 95Ω.

In some examples, the step of achieving the single shot isolation PVIsuccess rate includes achieving at least about 85% success rate byablating with a pre-ablation lowest initial anterior wall impedance ofbetween about 80-90Ω.

In some examples, the step of achieving the single shot isolation PVIsuccess rate includes achieving at least about 88% success rate byablating with a pre-ablation highest initial anterior wall impedance ofabout 110Ω.

In some examples, the step of achieving the single shot isolation PVIsuccess rate includes achieving at least about 87.5% success rate byablating with a pre-ablation initial anterior wall impedance variationimpedance range of less than about 20Ω.

In some examples, the characteristic is a predictor of the single shotisolation PVI success rate before ablation was limiting a highestinitial temperature to less than about 31° C. among the electrodes ofthe balloon catheter.

In some examples, the characteristic is a predictor of the single shotisolation PVI success rate before ablation was permitting a lowestanterior wall impedance between approximately about 80-90Ω.

In some examples, the step of achieving the single shot isolation PVIsuccess rate includes achieving at least about a 90% success rate byablating with a mean initial impedance of less than about 95Ω for and ahighest initial impedance of less than about 110Ω.

In some examples, the characteristic is a predictor is of the singleshot isolation PVI success rate before ablation, the predictor beinginitial temperature and impedance at a lesion site just before the stepof ablating.

In some examples, the characteristic is a predictor is of the singleshot isolation PVI success rate before ablation, the predictor beingrelatively low initial temperature (approximately 31 deg centigrade orunder) just before the step of ablating. The term “relatively lowinitial temperature” include a temperature lower than body temperatureand in one embodiment, approximately 31 degrees Centigrade or lower.

In some examples, the characteristic is a predictor is of the singleshot isolation PVI success rate before ablation, the predictor beinginitial temperature in a relatively low range with the highest andlowest impedance measured initially (before ablation) from theelectrodes being no more than 20-30 ohms (and preferably 20 ohms orless) apart (i.e., impedances measured from all the electrodes arewithin 20-30 (or less than 30) ohms of each other) at a lesion site justbefore the step of ablating.

In some examples, the characteristic is a predictor is of the singleshot isolation PVI success rate before ablation, the predictor beinginitial impedance having relatively high values with a relatively narrowrange.

In some examples, the characteristic is a predictor is of the singleshot isolation PVI success rate before ablation, the predictor beingabsolute values of impedance readings within a predetermined range.

In some examples, the characteristic is a predictor is of the singleshot isolation PVI success rate before and during ablation, thepredictor being electrode temperature before and during ablation.

In some examples, the characteristic is a predictor is of the singleshot isolation PVI success rate before ablation, the predictor beingmean initial temperature, and wherein the mean initial temperature isapproximately less than about 28° C. and the single shot isolation PVIsuccess rate is at least approximately about 90%.

In some examples, the characteristic is a predictor is of the singleshot isolation PVI success rate before ablation, the predictor being adistributed initial temperature, and wherein the distributed initialtemperature is approximately greater than about 31° C., and the singleshot isolation PVI success rate is at least approximately about 90%.

In some examples, the characteristic is a predictor is of the singleshot isolation PVI success rate before ablation, the predictor being adistributed initial temperature, and wherein the distributed initialtemperature is approximately greater than about 30° C., and the singleshot isolation PVI success rate is at least approximately about 90%.

In some examples, the characteristic is a predictor is of the singleshot isolation PVI success rate before ablation, the predictor being adistributed initial temperature, and wherein the distributed initialtemperature is approximately greater than about 29° C., and the singleshot isolation PVI success rate is at least approximately about 90%.

In some examples, the characteristic is a predictor is of the singleshot isolation PVI success rate before ablation, the predictor being apre-ablation lowest temperature slope, and wherein the pre-ablationlowest temperature slope is approximately greater than about 0.75°C./sec, and the single shot isolation PVI success rate is at leastapproximately about 90%.

In some examples, the characteristic is a predictor is of the singleshot isolation PVI success rate before ablation, the predictor being apre-ablation lowest value temperature, and wherein the pre-ablationlowest value temperature is approximately greater than about 6° C., andthe single shot isolation PVI success rate is at least approximatelyabout 90%.

In some examples, the characteristic is a predictor of the single shotisolation PVI success rate before ablation, the predictor being apre-ablation highest initial temperature, and wherein the pre-ablationhighest initial temperature is approximately less than about 31° C., andthe single shot isolation PVI success rate is at least approximatelyabout 90%.

In some examples, the characteristic is a predictor of the single shotisolation PVI success rate before ablation, the predictor being apre-ablation initial temperature variation, and wherein the pre-ablationinitial temperature variation is approximately less than about 3° C.,and the single shot isolation PVI success rate is at least approximatelyabout 95%.

In some examples, the characteristic is a predictor of the single shotisolation PVI success rate before ablation, the predictor being apre-ablation initial impedance variation, and wherein the pre-ablationinitial impedance variation comprises an optimal range of approximatelyless than about 20Ω, and the single shot isolation PVI success rate isat least approximately about 88.5%.

In some examples, the characteristic is a predictor of the single shotisolation PVI success rate before ablation, the predictor being apre-ablation lowest value impedance drop, and wherein the pre-ablationlowest value impedance drop is approximately greater than about 12Ω, andthe single shot isolation PVI success rate is at least approximatelyabout 90%.

In some examples, the characteristic is a predictor of the single shotisolation PVI success rate before ablation, the predictor being apre-ablation impedance drop variation, and wherein the pre-ablationimpedance drop variation is approximately greater than about 20Ω, andthe single shot isolation PVI success rate is at least approximatelyabout 85%.

In some examples, the characteristic is a predictor of the single shotisolation PVI success rate before ablation, the predictor being apre-ablation lowest value impedance drop percent, and wherein thepre-ablation lowest value impedance drop percent is greater than orequal to approximately about 12%, and the single shot isolation PVIsuccess rate is at least approximately about 90%.

In some examples, the characteristic is a predictor of the single shotisolation PVI success rate before ablation, the predictor being apre-ablation impedance drop percent variation, and wherein thepre-ablation impedance drop percent variation is less than about 20Ω,and the single shot isolation PVI success rate is at least approximatelyabout 85%.

In some examples, when a number of electrodes with initial impedancedeviation from mean value is zero, the single shot isolation PVI successrate is approximately about 92%.

In some examples, the characteristic is a predictor of the single shotisolation PVI success rate before ablation, the predictor being adifference of impedance between anterior and posterior wall.

In some examples, the difference is less than approximately about 20Ωand the single-shot PVI success rate is at least approximately about 85%for the predetermined patient population.

In some examples, the difference is less than approximately about 20Ωand the single-shot PVI success rate is at least approximately about 85%for the predetermined patient population of at least 25 patients.

In some examples, the difference is approximately between 20 to 30Ω andthe single-shot PVI success rate is at least approximately about 78% forthe predetermined patient population.

In some examples, the difference is approximately between 20 to 30Ω andthe single-shot PVI success rate is at least approximately about 78% forthe predetermined patient population of at least 75 patients.

In some examples, the difference is approximately between 30 to 40Ω andthe single-shot PVI success rate is at least approximately about 75% forthe predetermined patient population.

In some examples, the difference is approximately between 30 to 40Ω andthe single-shot PVI success rate is at least approximately about 75% forthe predetermined patient population of at least 60 patients.

In some examples, the difference is approximately between 40 to 50Ω andthe single-shot PVI success rate is at least approximately about 67% forthe predetermined patient population.

In some examples, the difference is approximately between 40 to 50Ω andthe single-shot PVI success rate is at least approximately about 67% fora predetermined patient population of at least 34 patients.

In some examples, the difference is approximately between 50 to 60Ω andthe single-shot PVI success rate is at least approximately about 35% forthe predetermined patient population.

In some examples, the difference is approximately between 50 to 60Ω andthe single-shot PVI success rate is at least approximately about 35% forthe predetermined patient population of at least 11 patients.

In some examples, the difference is greater than approximately about 60Ωand the single-shot PVI success rate is at least approximately about 33%for the predetermined patient population.

In some examples, the difference is greater than approximately about 60Ωand the single-shot PVI success rate is at least approximately about 33%for the predetermined patient population of at least 9 patients.

In some examples, the balloon catheter is a full-circle all electrodeburning ablation catheter.

In some examples, the step of ablating tissue is for a duration of 60seconds.

In some examples, the characteristic is a predictor of the single shotisolation PVI success rate before ablation, and wherein pre-ablationmean initial impedance is the predictor.

In some examples, the characteristic is a predictor of the single shotisolation PVI success rate before ablation, and wherein pre-ablationinitial impedance variation is the predictor.

In some examples, the characteristic is an evaluator of the single shotisolation PVI success rate post ablation, and wherein post-ablationlowest impedance drop is the evaluator.

In some examples, the characteristic is an evaluator of the single shotisolation PVI success rate post ablation, and wherein post-ablationimpedance drop variation is the evaluator.

In some examples, the characteristic is a predictor is of the singleshot isolation PVI success rate before ablation, and whereinpost-ablation mean temperature slope is the evaluator.

In some examples, the characteristic is an evaluator of the single shotisolation PVI success rate post ablation, and wherein post-ablationlowest temperature slope is the predictor.

In some examples, the characteristic is an evaluator of the single shotisolation PVI success rate post ablation, and wherein post-ablation meantemperature rise is the evaluator.

In some examples, the characteristic is an evaluator of the single shotisolation PVI success rate post ablation, and wherein post-ablationlowest temperature rise is the evaluator.

In some examples, the characteristic is an evaluator of the single shotisolation PVI success rate post ablation, and wherein post-ablationlowest impedance drop percentage is the evaluator.

In some examples, the characteristic is an evaluator of the single shotisolation PVI success rate post ablation, and wherein post-ablationvariation of impedance drop percentage is the evaluator.

In some examples, the characteristic is a predictor of the single shotisolation PVI success rate before ablation, and wherein pre-ablationlowest impedance drop is the predictor.

In some examples, the characteristic is a predictor of the single shotisolation PVI success rate before ablation, and wherein pre-ablationinitial temperature variation is the predictor.

In some examples, the characteristic is a predictor of the single shotisolation PVI success rate before ablation, and wherein pre-ablationmaximum initial impedance is the predictor.

In some examples, the characteristic is a predictor of the single shotisolation PVI success rate before ablation, and wherein pre-ablationmean initial anterior wall impedance is the predictor.

In some examples, the characteristic is a predictor of the single shotisolation PVI success rate before ablation, and wherein pre-ablationlowest anterior wall impedance is the predictor.

In some examples, the characteristic is a predictor of the single shotisolation PVI success rate before ablation, and wherein pre-ablationmaximum anterior wall impedance is the predictor.

In some examples, the characteristic is a predictor of the single shotisolation PVI success rate before ablation, and wherein pre-ablationanterior wall impedance variation is the predictor.

In some examples, impedance values were among the electrodes of theanterior wall.

In some examples, the characteristic is a predictor of the single shotisolation PVI success rate before ablation, and wherein the predictor isdetermined by:

${Probability}\text{∼∼}\frac{e^{Y}}{( {1 + e^{Y}} )}$Y∼∼4.367 − 0.420Δ T₀ − 0.0486Δ Z₀

wherein ΔT₀ is initial impedance variation and ΔZ₀ is initialtemperature variation. In some examples, the characteristic is apredictor of the single shot isolation PVI success rate before ablation,and wherein the predictor is determined by:

${Prob}\text{∼∼}\frac{e^{Y}}{( {1 + e^{Y}} )}$Y ∼ 26.78 − 0.576T_(0 max ) − 0.0632Z_(0 max )

wherein T_(0max) is highest initial temperature and Z_(0max) is highestinitial impedance.

In some examples, the characteristic is a predictor of the single shotisolation PVI success rate before ablation, and wherein the predictor isdetermined by:

${Prob} \sim \frac{e^{Y}}{( {1 + e^{Y}} )}$Y ∼ 27.70 − 0.540T_(0 max ) − 0.09595Z_(0 max )

wherein T_(0max) is highest initial temperature and Z_(0max) is highestinitial impedance.

In some examples, the characteristic is a predictor of the single shotisolation PVI success rate before ablation, and wherein the predictor isdetermined by:

${Prob} \sim \frac{e^{Y}}{( {1 + e^{Y}} )}$Y ∼ 9.31 − 0.408Δ T₀ − 0.0544Z_(0 max )

wherein ΔT₀ is initial temperature variation and Z_(0max) is highestinitial impedance.

In some examples, the characteristic is a predictor of the single shotisolation PVI success rate before ablation, and wherein the predictor isdetermined by:

${Prob} \sim \frac{e^{Y}}{( {1 + e^{Y}} )}$Y ∼ 22.61 − 0.622T_(0 max ) − 0.0626Z₀ 

wherein T_(0max) is highest initial temperature and ΔZ₀ is initialimpedance variation.

In some examples, the characteristic is a predictor of the single shotisolation PVI success rate before ablation, and wherein the predictor isdetermined by:

${Prob} \sim \frac{e^{Y}}{( {1 + e^{Y}} )}$Y ∼ 11.53 − 0.439Δ T₀ − 0.0856  Z_(0 mean)

wherein ΔT₀ is initial temperature variation and Z_(0max) is meaninitial impedance

In some examples, the characteristic is a predictor of the single shotisolation PVI success rate before ablation, and wherein the predictor isdetermined by:

${Prob} \sim \frac{e^{Y}}{( {1 + e^{Y}} )}$Y ∼ 26.52 + 0.013Δ T₀ − 0.594T_(0 max ) − 0.0122Δ Z₀ − 0.0535Z_(0 max )

wherein ΔT₀ is initial temperature variation, T_(0max) is highestinitial temperature, ΔZ₀ is initial impedance variation, and Z_(0max) ishighest initial impedance.

In some examples, the characteristic is an evaluator of the single shotisolation PVI success rate post ablation, and wherein the evaluator isdetermined by:

${Prob} \sim \frac{e^{Y}}{( {1 + e^{Y}} )}$Y ∼ 1.562 + 0.2856T_(min) − 0.0629 Δ Z_(drop)

wherein ΔT_(min) is lowest temperature rise and ΔZ_(drop) is impedancedrop variation.

In some examples, the characteristic is an evaluator of the single shotisolation PVI success rate post ablation, and wherein the evaluator isdetermined by:

${Prob} \sim \frac{e^{Y}}{( {1 + e^{Y}} )}$Y ∼ −0.644 + 0.170 Δ T_(min) + 0.107  Z_(drop )%_(min)

wherein ΔT_(min) is lowest temperature rise and Z_(drop)%_(min) islowest impedance drop percent.

In some examples, the characteristic is an evaluator of the single shotisolation PVI success rate post ablation, and wherein the evaluator isdetermined by:

$P\text{∼}\frac{e^{Y}}{( {1 + e^{Y}} )}$Y∼0.339 + 0.187 Δ T_(min) + 0.0737  Z_(drop )  %_(min) − 0.0368 Δ Z_(drop)  %

wherein ΔT_(min) is lowest temperature rise, Z_(drop)%_(min) is lowestimpedance drop percent, and Δ Z_(drop)%) is impedance drop percentvariation.

In some examples, the characteristic is an evaluator of the single shotisolation PVI success rate post ablation, and wherein the evaluator isdetermined by:

$P\text{∼}\frac{e^{Y}}{( {1 + e^{Y}} )}$Y∼1.043 + 0.777T_(min)^(′) + 0.171Δ T_(min) + 0.0479  Z_(drop − min ) − 0.0589 Δ Z_(drop)

wherein T′_(min) is lowest temperature slope, ΔT_(min) is lowesttemperature rise, Z_(drop-min) is lowest impedance drop and ΔZ_(drop) isimpedance drop variation.

In some examples, the characteristic is an evaluator of the single shotisolation PVI success rate post ablation, and wherein the evaluator isdetermined by:

$P\text{∼}\frac{e^{Y}}{( {1 + e^{Y}} )}$Y∼ − 0.507 + 0.206Δ T_(min) + 0.083  Z_(dropmin)

wherein ΔT_(min) is lowest temperature rise and Z_(dropmin) is minimumimpedance drop.

In some examples, the characteristic is an evaluator of the single shotisolation PVI success rate post ablation, and wherein the evaluator isdetermined by:

$P\text{∼}\frac{e^{Y}}{( {1 + e^{Y}} )}$Y∼1.248 + 0.2486 Δ T_(min) − 0.0594  Δ Z_(drop) + 0.0419  Z_(dropmin)wherein ΔT_(min) is lowest temperature rise and Z_(dropmin) is minimumimpedance drop.

In some examples, the characteristic is an evaluator of the single shotisolation PVI success rate post ablation, and wherein the evaluator isdetermined by:

$P\text{∼}\frac{e^{Y}}{( {1 + e^{Y}} )}$Y∼1.174 + 0.2515 Δ T_(min) − 0.0564 Δ Z_(drop)  %

wherein ΔT_(min) is lowest temperature rise and Δ Z_(drop) is impedancedrop percent variation.

In some examples, the method or use includes a step of displaying agraphical representation of the independently controllable electrodesand the ablation parameters.

In some examples, one ablation parameter comprises impedance measuredproximate each electrode.

In some examples, the measured impedance comprises impedance measuredbefore ablation.

In some examples, the measured impedance comprises impedance measuredafter ablation.

In some examples, the measured impedance comprises impedance measuredbefore and impedance measured after ablation.

In some examples, one ablation parameter comprises temperature measuredproximate each electrode.

In some examples, one ablation parameter comprises a maximum temperaturemeasured proximate each electrode during the ablating.

In some examples, one ablation parameter comprises a measuredtemperature rise from a beginning of ablating to an end of the ablating.

In some examples, a method or use is disclosed to treat a plurality ofpatients for paroxysmal atrial fibrillation. The method or use caninclude delivering a multi-electrode radiofrequency balloon catheter anda multi-electrode diagnostic catheter to one or more targeted pulmonaryveins; ablating tissue of the one or more targeted pulmonary veins usingthe multi-electrode radiofrequency balloon catheter; diagnosing the oneor more targeted pulmonary veins using the multi-electrode diagnosticcatheter; and achieving at least one of a predetermined clinicaleffectiveness and acute effectiveness of the procedure based on use ofthe multi-electrode radiofrequency balloon catheter and themulti-electrode diagnostic catheter in the isolation of the one or moretargeted pulmonary veins.

In some examples, the acute effectiveness is defined by confirming ifthere is an entrance block in all targeted pulmonary veins afteradenosine and/or isoproterenol challenge.

In some examples, the acute effectiveness is further defined by successgreater than 90% for the plurality of patients.

In some examples, the acute effectiveness is further defined by successgreater than 95% for the plurality of patients.

In some examples, a Type-1 error rate for power the acute effectivenessand the clinical effectiveness of all targeted veins are controlled atapproximately a 5% level. The method or use can include determiningwhether the procedure is clinically successful for the plurality ofpatients if both the acute effectiveness and the clinical effectivenessindications are controlled at approximately the 5% level.

In some examples, the acute effectiveness is at least 80% for theplurality of patients being at least 80 patients, 130 patients, and/or230 patients.

In some examples, the acute effectiveness is further defined byconfirming if there is an entrance block in all targeted pulmonary veinsafter adenosine and/or isoproterenol challenge using a focal ablationcatheter.

In some examples, the acute effectiveness is further defined byconfirming if there is an entrance block in all targeted pulmonary veinsafter adenosine and/or isoproterenol challenge without using a focalablation catheter.

In some examples, the procedure is administered on the plurality ofpatients diagnosed with symptomatic paroxysmal atrial fibrillation.

In some examples, the predetermined effectiveness rate is defined by anaverage number of RF applications per patient and RF time required toisolate all pulmonary veins the step of diagnosing further comprises:electrophysiological mapping of the heart.

In some examples, the multi-electrode diagnostic catheter furthercomprises a high torque shaft with a halo-shaped tip section containinga plurality of pairs of electrodes visible under fluoroscopy.

In some examples, the predetermined acute effectiveness is defined byulceration being absent in the plurality of patients after theprocedure.

In some examples, the predetermined acute effectiveness is defined by acomplication rate of approximately 13% or fewer of the plurality ofpatients experiencing esophageal erythema after the procedure.

In some examples, the predetermined acute effectiveness is defined by acomplication rate of approximately 25% or fewer of the plurality ofpatients experiencing new asymptomatic cerebral embolic lesions afterthe procedure.

In some examples, the predetermined acute effectiveness is defined by acomplication rate of approximately 20% or fewer of the plurality ofpatients experiencing new asymptomatic cerebral embolic lesions afterthe procedure.

In some examples, wherein the predetermined acute effectiveness isdefined by a complication rate of approximately 5-9% or fewer of theplurality of patients experiencing a primary adverse event byapproximately 7 or more days after the procedure.

In some examples, inclusion criteria for the plurality of patientsincludes a diagnosis with symptomatic paroxysmal atrial fibrillation anda patient capability to comply with uninterrupted per-protocolanticoagulation requirements.

In some examples, the predetermined acute effectiveness is defined by atotal procedure time.

In some examples, a population size for the predetermined success rateis at least 80 patients, 130 patients, 180 patients, and/or 230patients.

In some examples, the predetermined acute effectiveness is defined by atotal RF application time.

In some examples, the predetermined acute effectiveness is defined by atotal dwell time of the multi-electrode radiofrequency balloon catheter.

In some examples, the predetermined acute effectiveness is defined by atotal time to isolate all targeted pulmonary veins.

In some examples, the predetermined acute effectiveness is defined by anumber and a total time of applications by the multi-electroderadiofrequency balloon catheter per location of all targeted pulmonaryveins.

In some examples, the predetermined acute effectiveness is defined by anumber and a total time of applications by the multi-electroderadiofrequency balloon catheter per patient.

In some examples, the predetermined acute effectiveness is defined by anumber and a total time of applications by the multi-electroderadiofrequency balloon catheter per targeted vein.

In some examples, multi-electrode radiofrequency balloon cathetercomprises a compliant balloon with a plurality of electrodes bondedconfigured to deliver RF energy to tissue of the pulmonary vein andsense temperature at each electrode.

In some examples, clinical effectiveness is defined by an incidence ofearly onset of one or more adverse events within a predetermined time ofthe procedure being implemented.

In some examples, the predetermined time is at least 7 days.

In some examples, the one or more adverse events comprise: death,atrio-esophageal fistula, myocardial infarction, cardiactamponade/perforation, thromboembolism, stroke, TIA (Transient IschemicAttack), phrenic nerve paralysis, pulmonary vein stenosis, and the majorvascular access bleeding.

In some examples, the one or more adverse events comprise: incidence ofindividual adverse events from a primary composite; incidence of seriousadverse device effect; incidence of serious adverse events within 7days, at least 7¬30 days, and at least 30 days following the procedure;incidence of non-serious adverse events; incidence of pre- andpost-ablation asymptomatic and symptomatic cerebral emboli as determinedby MRI evaluation; and frequency, anatomic location, and size (diameterand volume) of cerebral emboli by MRI evaluations at baseline,post-ablation and during follow-up.

In some examples, the one or more adverse events for approximately 8% ofthe plurality of patients, the one or more adverse events comprising:NIHSS (National Institute of Health Stroke Scale) scores at baseline,post-ablation and during follow-up; a summary of MoCA (MontrealCognitive Assessment) and mRS (Modified Ranking Scale) scores atbaseline, 1 month and during further follow-up; a rate ofhospitalization for cardiovascular events; a percentage (%) of pulmonaryvein isolation touch-up by focal catheter among the one or more targetedveins; a percentage (%) of subjects with use of focal catheter ablationsfor non-PV triggers; a percentage (%) of subjects with freedom fromdocumented symptomatic atrial fibrillation (AF), atrial tachycardia(AT), or atypical (left side) atrial flutter (AFL) episodes(episodes >30 seconds on arrhythmia monitoring device from day 91 to180); a percentage (%) of subjects with freedom from documented atrialfibrillation (AF), atrial tachycardia (AT), or atypical (left side)atrial flutter (AFL); one or more episodes that endure for 30 or moreseconds on an arrhythmia monitoring device from day 91 to 180 followingthe procedure; and one or more procedural parameters including totalprocedure and ablation time, balloon dwell time, RF application time, anumber of RF applications, fluoroscopy time and dose.

In some examples, the acute safety rate includes complication rates of10% or less and is defined by incidence of asymptomatic cerebral emboliclesions at a discharge magnetic resonance imaging (MRI).

In some examples, the acute effectiveness rate includes complicationrates of approximately 0% and is defined by existence of esophagealinjury erythema.

In some examples, the acute effectiveness rate is 100% and is defined byelectrically isolating all targeted pulmonary veins without use of afocal ablation catheter.

In some examples, the acute effectiveness rate is defined by a freedomfrom documented atrial fibrillation, atrial tachycardia, or atypicalatrial flutter episodes based on electrocardiographic data through aneffectiveness evaluation period (1 year).

In some examples, the acute effectiveness rate is defined by pulmonaryvein isolation touch-up by a focal catheter among all targeted pulmonaryveins.

In some examples, the predetermined clinical effectiveness rate isdefined by 10% or less complication rates related to incidence ofpost-ablation symptomatic and asymptomatic cerebral emboli as comparedto pre-ablation.

In some examples, the multi-electrode diagnostic catheter is configuredfor electrophysiological recording and stimulation of the atrial regionof the heart and is used in conjunction with the multi-electroderadiofrequency balloon catheter.

In some examples, a method or use of administering a procedure to treata plurality of patients for paroxysmal atrial fibrillation. The methodor use includes delivering a multi-electrode radiofrequency ballooncatheter and a multi-electrode diagnostic catheter to one or moretargeted pulmonary veins; and ablating tissue of all targeted pulmonaryveins using the multi-electrode radiofrequency balloon catheter;diagnosing all targeted pulmonary veins using the multi-electrodediagnostic catheter; and achieving a predetermined rate of adverseevents, using the multi-electrode radiofrequency balloon catheter andthe multi-electrode diagnostic catheter in the isolation of all targetedpulmonary veins, during and approximately 6 months after the procedure.

In some examples, a method or use of treating a plurality of patientsfor paroxysmal atrial fibrillation. The method or use includesevaluating a number and size of all targeted pulmonary veins and anatomyof the left atrial; puncturing the transseptal; selectively positioninga multi-electrode esophageal temperature monitoring device in thevasculature with respect to all targeted pulmonary veins; selectivelypositioning a multi-electrode radiofrequency balloon catheter in thevasculature with respect to all targeted pulmonary veins; selectivelypositioning a multi-electrode diagnostic catheter in the vasculaturewith respect to all targeted pulmonary veins; ablating tissue of alltargeted pulmonary veins using the multi-electrode radiofrequencyballoon catheter; confirming isolation of all targeted pulmonary veinsusing the multi-electrode diagnostic catheter; confirming existence ofan entrance block in all targeted pulmonary veins; achieving apredetermined clinical effectiveness and/or acute effectiveness of theprocedure, based on the confirmed existence of the entrance block,regarding the isolation of all targeted pulmonary veins following theprocedure.

In some examples, mapping all targeted pulmonary veins using thediagnostic catheter.

In some examples, exclusion criteria for the plurality of patientscomprises at least one of the following: atrial fibrillation secondaryto electrolyte imbalance, thyroid disease, or reversible or non-cardiaccause; previous surgical or catheter ablation for atrial fibrillation;anticipated to receive ablation outside all targeted pulmonary veinsostia and CTI region; previously diagnosed with persistent, longstandingatrial fibrillation and/or continuous atrial fibrillation >7 days,or >48 hrs terminated by cardioversion; any percutaneous coronaryintervention (PCI) within the past 2 months; valve repair or replacementand presence of a prosthetic valve; any carotid stenting orendarterectomy; coronary artery bypass grafting, cardiac surgery,valvular cardiac surgical or percutaneous procedure within the past 6months; documented left atrium thrombus on baseline imaging; LA anteroposterior diameter greater than 50 mm; any pulmonary vein with adiameter greater than or equal to 26 mm; left ventricular ejectionfraction less than 40%; contraindication to anticoagulation; history ofblood clotting or bleeding abnormalities; myocardial infarction withinthe past 2 months; documented thromboembolic event within the past 12months; rheumatic heart disease; awaiting cardiac transplantation orother cardiac surgery within the next 12 months; unstable angina; acuteillness or active systemic infection or sepsis; diagnosed atrial myxomaor interatrial baffle or patch; presence of implanted pacemaker,implantable cardioverter defibrillator, tissue-embedded, oriron-containing metal fragments; significant pulmonary disease or anyother disease or malfunction of the lungs or respiratory system thatproduces chronic symptoms; significant congenital anomaly; pregnancy orlactating; enrollment in an investigational study evaluating anotherdevice, biologic, or drug; pulmonary vein stenosis; presence ofintramural thrombus, tumor or other abnormality that precludes vascularaccess, or manipulation of the catheter; presence of an IVC filter;presence of a condition that precludes vascular access; life expectancyor other disease processes likely to limit survival to less than 12months; contraindication to use of contrast agents for MRI; presence ofiron-containing metal fragments in the patient; or unresolvedpre-existing neurological deficit.

In some examples, the multi-electrode radiofrequency balloon catheterincludes a compliant balloon with a plurality of electrodes configuredto deliver RF energy to tissue of all targeted pulmonary veins and sensetemperature at each electrode. In some examples, the plurality ofelectrodes is oriented circularly to circumferentially contact with anostia of the pulmonary vein. In some examples, the method or useincludes using the plurality of electrodes for visualization,stimulation, recording, and ablation. In some examples, each electrodeis configured so an amount of power delivered to each electrode iscontrolled independently. In some examples, the multi-electroderadiofrequency balloon catheter further comprises a proximal handle, adistal tip, and a middle section disposed therebetween. In someexamples, the proximal handle is a deflection thumb knob allowing forunidirectional deflection, a balloon advancement mechanism, and a luerfitting for balloon inflation and irrigation. In some examples, themulti-electrode radiofrequency balloon catheter further comprises ahigh-torque shaft configured to be rotated to facilitate accuratepositioning of the catheter tip to a desired; and a unidirectionalbraided deflectable tip section.

In some examples, the method or use also includes controlling irrigationto the multi-electrode radiofrequency balloon catheter with anirrigation pump.

In some examples, the method or use also includes administeringuninterrupted anticoagulation therapy at least 1 month prior to theprocedure.

In some examples, if the patient is receiving warfarin/coumadin therapy,the patient must have an international normalized ratio (INR)≥2 for atleast 3 weeks prior to the procedure.

In some examples, if the patient is receiving warfarin/coumadin therapy,the patient must be confirmed to have an international normalized ratio(INR)≥2 within 48 hours pre-procedure.

In some examples, the method or use also includes continuinganticoagulation therapy prior to the procedure.

In some examples, the method or use also includes administering atransseptal puncture; confirming an activated clotting time target of≥350 sec. prior to inserting the multi-electrode radiofrequency ballooncatheter into the left atrium and maintaining throughout the procedure;introducing the multi-electrode radiofrequency balloon catheter;introducing of a multi-electrode circular diagnostic catheter; ablatingthe pulmonary vein with the multi-electrode radiofrequency ballooncatheter; determining in real time pulmonary vein isolation with themulti-electrode circular diagnostic catheter; and confirming whether anentrance is blocked in the pulmonary vein.

In some examples, the method or use also includes the multi-electrodecircular diagnostic catheter comprises: an elongated body having alongitudinal axis; a distal assembly distal the elongated body, thedistal assembly having a helical form comprising a proximal loop and adistal loop, and a shape-memory support member extending through atleast the proximal loop, the proximal loop and the distal loop beingoriented obliquely at an angle relative to the longitudinal axis of theelongated body; at least one irrigated ablation ring electrode mountedon the proximal loop; a control handle proximal the elongated body; anda contraction wire having a proximal end in the control handle and adistal end anchored in the proximal loop, the control handle including afirst control member configured to actuate the contraction wire tocontract the proximal loop, wherein the proximal loop has a firstflexibility and the distal loop has a second flexibility, and the secondflexibility is greater than the first flexibility.

In some examples, a method or use of treating a plurality of patientsfor paroxysmal atrial fibrillation by applying energy to tissue of asubject's heart proximate to an esophagus, phrenic nerve, or lung, themethod or use comprising the steps of achieving at least one of apredetermined clinical effectiveness and acute effectiveness of theprocedure based on use of a multi-electrode radiofrequency ballooncatheter and a multi-electrode diagnostic catheter in the isolation ofthe one or more targeted pulmonary veins by positioning an expandablemember proximate to the left atrium, the expandable member of themulti-electrode radiofrequency balloon catheter having a longitudinalaxis and including a plurality of electrodes disposed about thelongitudinal axis, each electrode capable of being energizedindependently, the plurality of electrodes including a first electrodehaving a first radiopaque marker and a second electrode having a secondradiopaque marker different from the first radiopaque marker; viewing animage of the expandable member as well as the first and secondradiopaque markers in the left atrium; determining an orientation of thefirst and second radiopaque markers with respect to a portion of theleft atrium closest to the esophagus, phrenic nerve, or lung, of thesubject; moving one of the first and second radiopaque markers to aportion of the left atrium closest to the esophagus, phrenic nerve orlung; energizing one or more electrodes indexed to the one of theradiopaque markers proximate the portion close to the esophagus, phrenicnerve, or lung, at a lower energization setting as compared to otherelectrodes to create a transmural lesion in the left atrium with littleor no effect to adjacent anatomical structures; andelectrophysiologically recording and stimulating the atrial region ofthe tissue proximate to the esophagus, phrenic nerve, or lung using themulti-electrode diagnostic catheter.

In some examples, a clinically effective device is disclosed to treatatrial fibrillation in a group of patients. The device can include anend probe coupled to a tubular member that extends along a longitudinalaxis from a proximal portion to a distal portion. The end probe caninclude a first expandable membrane coupled to the tubular member; aplurality of electrodes disposed generally equiangularly about thelongitudinal axis on an outer surface of the first expandable membrane;at least one wire connected each of the plurality of electrodes, the atleast one wire of each electrode extending from the first expandablemembrane toward the tubular member; and a second expandable membranethat encapsulates a portion of the at least one wire between the secondexpandable membrane and the first expandable membrane. The device canachieve a predetermined effectiveness rate of pulmonary vein isolationin the group of patients.

In some examples, a clinically effective device is disclosed toadminister a procedure for cardiac electrophysiological ablation ofpulmonary veins of the atria and treatment of drug refractory recurrentsymptomatic pulmonary atrial fibrillation. The device can include an endprobe coupled to a tubular member that extends along a longitudinal axisfrom a proximal portion to a distal portion. The end probe can include afirst expandable membrane coupled to the tubular member; a plurality ofelectrodes disposed generally equiangularly about the longitudinal axison an outer surface of the first expandable membrane; at least one wireconnected each of the plurality of electrodes, the at least one wire ofeach electrode extending from the first expandable membrane toward thetubular member; and a second expandable membrane that encapsulates aportion of the at least one wire between the second expandable membraneand the first expandable membrane so that each of the plurality ofelectrodes is independently controlled to achieve a predeterminedeffectiveness rate of pulmonary vein isolation.

In some examples, a clinically effective device is disclosed toadminister a procedure for cardiac electrophysiological ablation ofpulmonary veins of the atria and treatment of drug refractory recurrentsymptomatic pulmonary atrial fibrillation. The device can include an endprobe coupled to a tubular member that extends along a longitudinal axisfrom a proximal portion to a distal portion. The end probe can include afirst expandable membrane coupled to the tubular member; a plurality ofelectrodes disposed generally equiangularly about the longitudinal axison an outer surface of the first expandable membrane; at least one wireconnected each of the plurality of electrodes, the at least one wire ofeach electrode extending from the first expandable membrane toward thetubular member; and a second expandable membrane that encapsulates aportion of the at least one wire between the second expandable membraneand the first expandable membrane so that each of the plurality ofelectrodes is independently controlled to achieve pulmonary veinisolation and at least a 97% safety endpoint within seven (7) days ofsuccessful pulmonary vein isolation.

In some examples, a clinically effective device is disclosed toadminister a procedure for cardiac electrophysiological ablation ofpulmonary veins of the atria and treatment of drug refractory recurrentsymptomatic pulmonary atrial fibrillation. The device can include an endprobe coupled to a tubular member that extends along a longitudinal axisfrom a proximal portion to a distal portion. The end probe can include afirst expandable membrane coupled to the tubular member; a plurality ofelectrodes disposed generally equiangularly about the longitudinal axison an outer surface of the first expandable membrane; at least one wireconnected each of the plurality of electrodes, the at least one wire ofeach electrode extending from the first expandable membrane toward thetubular member; and a second expandable membrane that encapsulates aportion of the at least one wire between the second expandable membraneand the first expandable membrane so that each of the plurality ofelectrodes is independently controlled to achieve pulmonary veinisolation and at least a 90% safety endpoint within seven (7) days ofsuccessful pulmonary vein isolation.

In some examples, the predetermined effectiveness rate includescomplication rates of 10% or less and is defined by existence ornon-existence of asymptomatic cerebral embolic lesions at a dischargemagnetic resonance imaging (MRI).

In some examples, the predetermined effectiveness rate includescomplication rates of approximately 0% and is defined by existence ornon-existence of esophageal injury erythema.

In some examples, the predetermined effectiveness rate is approximately100% and is defined by electrically isolating all targeted pulmonaryveins without use of a focal ablation catheter.

In some examples, the predetermined effectiveness rate is defined by afreedom from documented atrial fibrillation, atrial tachycardia, oratypical atrial flutter episodes based on electrocardiographic datathrough an effectiveness evaluation period. In some examples, theeffectiveness evaluation period is approximately one year.

In some examples, the predetermined effectiveness rate is defined bypulmonary vein isolation touch-up by a focal catheter among all targetedpulmonary veins.

In some examples, the predetermined effectiveness rate is defined byusing focal catheter ablation for non-PV triggers during the indexprocedure.

In some examples, the predetermined effectiveness rate comprises along-term effectiveness rate.

In some examples, the predetermined effectiveness rate is defined by anaverage number of Radio-Frequency applications per patient andRadio-Frequency time required to isolate all pulmonary veins.

In some examples, the predetermined effectiveness rate is defined by anaverage number of Radio-Frequency applications per vein andRadio-Frequency time required to isolate common pulmonary veins.

In some examples, the predetermined effectiveness rate is defined by anaverage number of Radio-Frequency applications per patient andRadio-Frequency time required to isolate common pulmonary veins.

In some examples, the predetermined effectiveness rate is defined bydetermining incidence of complication rates being 10% or less ofpost-ablation symptomatic and asymptomatic cerebral emboli as comparedto pre-ablation.

In some examples, the predetermined effectiveness rate is defined byevaluating a presence of emboli-associated neurological deficits by atleast one of NIHSS and mRS assessments.

In some examples, the end probe is configured for use in catheter-basedcardiac electrophysiological mapping of the atria.

In some examples, the end probe is configured for cardiac ablation.

In some examples, the end probe comprises: the plurality of electrodesbonded to the first expandable membrane and configured to deliverRadio-Frequency energy to tissue of the pulmonary vein and sensetemperature at each electrode.

In some examples, the plurality of electrodes is oriented circularly tocircumferentially contact with an ostia of the pulmonary vein.

In some examples, the device is further configured for using theplurality of electrodes for visualization, stimulation, recording, andablation.

In some examples, each electrode is configured so an amount of powerdelivered to each electrode is controlled independently.

In some examples, the end probe further comprises a proximal handle, adistal tip, and a middle section disposed therebetween.

In some examples, the proximal handle is a deflection thumb knoballowing for unidirectional deflection, a balloon advancement mechanism,and a luer fitting for balloon inflation and irrigation.

In some examples, the end probe further includes a high-torque shaftconfigured to be rotated to facilitate accurate positioning of thecatheter tip to a desired; and a unidirectional braided deflectable tipsection.

In some examples, the end probe further includes a first substratedisposed on the membrane, the first substrate including a firstradiopaque marker of a first form disposed thereon; and a secondsubstrate disposed on the membrane, the second substrate including asecond radiopaque marker of a second form disposed thereon, the secondform being different from the first form.

In some examples, the device further includes an irrigation pump toprovide irrigation fluid to the first expandable membrane and out of thefirst expandable membrane.

In some examples, the effectiveness evaluation period is at least 91days following a delivery of the end probe to the pulmonary vein; andablation of tissue proximate the pulmonary vein with the end probe.

In some examples, the effectiveness evaluation period is less than orequal to one year following a delivery of the end probe to the pulmonaryvein; and ablation of tissue proximate the pulmonary vein with the endprobe.

In some examples, the predetermined success rate is 60% for a populationsize of at least 40 patients.

In some examples, a population size for the predetermined success rateis at least 300 patients, 200 patients, 100 patients, or 50 patients.

In some examples, the predetermined success rate is at least 60%.

In some examples, the predetermined success rate is determined byevaluation of the patient 7 days following a delivery of the end probeto the pulmonary vein and ablation of tissue proximate the pulmonaryvein with the end probe.

In some examples, the predetermined success rate is determined byevaluation of the patient 1 month following a delivery of the end probeto the pulmonary vein; and ablation of tissue proximate the pulmonaryvein with the end probe.

In some examples, the predetermined success rate is determined byevaluation of the patient 6 months following a delivery of the end probeto the pulmonary vein; and ablation of tissue proximate the pulmonaryvein with the end probe.

In some examples, the predetermined success rate is determined byevaluation of the patient 12 months following a delivery of the endprobe to the pulmonary vein; and ablation of tissue proximate thepulmonary vein with the end probe.

In some examples, the predetermined success rate further includesconfirmation of an entrance block in the pulmonary vein after at leastone of adenosine and isoproterenol challenge.

In some examples, the patient suffering at least one of the followingevents is deemed as an unsuccessful pulmonary vein isolation, including:device or procedure related death; atrio-esophageal fistula, myocardialinfarction; cardiac Tamponade/Perforation; thromboembolism;stroke/Cerebrovascular Accident (CVA); transient Ischemic Attach (TIA);phrenic Nerve Paralysis, Pulmonary Vein Stenosis; pericarditis;pulmonary Edema; major Vascular Access Complication/Bleeding; andhospitalization (initial or prolonged).

In some examples, the patient suffering at least one of the followingevents is deemed as an unsuccessful pulmonary vein isolation, wherebythose events can include acute procedural failure; repeat ablation orsurgical treatment for AF/AT/Atypical (left-side) AFL after the blankingperiod (after day 90 post index procedure); DC cardioversion forAF/AT/Atypical (left-side) AFL, continuous AF/AT/AFL on a standard12-lead ECG even if the recording is less than 30 seconds in duration(after day 90 post index procedure); a new Class I and/or Class III AADis prescribed for AF during effectiveness evaluation period (day 91-365post index procedure) or prescribed during the blanking period andcontinued past 90 days; a previously failed Class I and/or Class III AAD(failed at or before screening) is taken for AF at a greater dose thanthe highest ineffective historical dose during the effectivenessevaluation period; and amiodarone is prescribed post procedure.

In some examples, the safety endpoint is defined by a patient sufferinga primary adverse event.

In some examples, at least one risk factor for the patient can beselected as: at least three (3) symptomatic episodes of atrialfibrillation that last lasting ≥1 minute within six (6) months beforethe device; at least one (1) atrial fibrillation episodeelectrocardiographically documented within twelve (12) months prior toenrollment (e.g., electrocardiogram (ECG), Holter monitor, telemetrystrip, etc.); failing at least one (1) Class I or Class III AAD asevidenced by recurrent symptomatic atrial fibrillation or intolerableside effects to the AAD; age under 18 and 75 or over; secondary toelectrolyte imbalance; thyroid disease; reversible or non-cardiac cause;and previous surgical or catheter ablation for atrial fibrillation.

In some examples, for purposes of calculating the effectiveness rate,the patient has at least one of the following risk factors: patientsknown to require ablation outside the PV ostia and CTI region;previously diagnosed with persistent or long-standing persistent atrialfibrillation and/or continuous atrial fibrillation 7 days following thedevice procedure; any percutaneous coronary intervention within the past2 months; repair or replacement or presence of a prosthetic valve; anycarotid stenting or endarterectomy within the past 6 months; coronaryartery bypass grafting, cardiac surgery or valvular cardiac surgicalprocedure within the past 6 months; documented left atrium thrombuswithin 1 day prior to the device procedure; left atrium antero posteriordiameter >50 mm; left Ventricular Ejection Fraction <40%;contraindication to anticoagulation; history of blood clotting orbleeding abnormalities; myocardial infarction within the past 2 months;documented thromboembolic event (including transient ischemic attack)within the past 12 months; Rheumatic Heart Disease; Uncontrolled heartfailure or New York Heart Association (NYHA) function class III or IV;awaiting cardiac transplantation or other cardiac surgery within thenext 12 months; unstable angina; acute illness or active systemicinfection or sepsis; diagnosed atrial myxoma or presence of aninteratrial baffle or patch; presence of implanted pacemaker orimplantable cardioverter defibrillator (ICD); significant pulmonarydisease or any other disease or malfunction of the lungs or respiratorysystem that produces chronic symptoms; significant congenital anomaly;women who are pregnant; enrollment in an investigational studyevaluating another device, biologic, or drug; known pulmonary veinstenosis; presence of intramural thrombus, tumor or other abnormalitythat precludes vascular access, or manipulation of the catheter;presence of an inferior vena cava filter; presence of a condition thatprecludes vascular access; life expectancy or other disease processeslikely to limit survival to less than 12 months; presentingcontra-indication for the devices; and patient on amiodarone at any timeduring the past 3 months prior to enrollment.

In some examples, if the patient is receiving warfarin/coumadin therapy,the patient must have an international normalized ratio ≥2 for at least3 weeks prior to the procedure.

In some examples, if the patient is receiving warfarin/coumadin therapy,the patient must be confirmed to be ≥2 within 48 hours pre-procedure.

In some examples, wherein anticoagulation therapy is provided prior tothe procedure.

In some examples, wherein an activated clotting time of 350-400 secondsis targeted prior to insertion of the catheter and throughout theprocedure.

In some examples, wherein an activated clotting time levels are checkedevery 15-30 minutes during the procedure to ensure an activated clottingtime target of 350-400 seconds.

In some examples, wherein the multi-electrode circular diagnosticcatheter includes an elongated body having a longitudinal axis and adistal assembly distal the elongated body. The distal assembly can havea helical form comprising a proximal loop, a distal loop, and ashape-memory support member extending through at least the proximalloop. The proximal loop and the distal loop can be oriented obliquely atan angle relative to the longitudinal axis of the elongated body; atleast one irrigated ablation ring electrode mounted on the proximalloop; a control handle proximal the elongated body; and a contractionwire having a proximal end in the control handle and a distal endanchored in the proximal loop, the control handle including a firstcontrol member configured to actuate the contraction wire to contractthe proximal loop. The proximal loop can have a first flexibility andthe distal loop has a second flexibility, and the second flexibility canbe greater than the first flexibility.

To the accomplishment of the foregoing and related ends, certainillustrative aspects are described herein in connection with thefollowing description and the appended drawings. These aspects areindicative, however, of but a few of the various ways in which theprinciples of the claimed subject matter can be employed and the claimedsubject matter is intended to include all such aspects and theirequivalents. Other advantages and novel features can become apparentfrom the following detailed description when considered in conjunctionwith the drawings.

BRIEF DESCRIPTION OF THE DRAWINGS

The above and further aspects of this invention are further discussedwith reference to the following description in conjunction with theaccompanying drawings, in which like numerals indicate like structuralelements and features in various figures. The drawings are notnecessarily to scale, emphasis instead being placed upon illustratingprinciples of the invention. The figures depict one or moreimplementations of the inventive devices, by way of example only, not byway of limitation.

FIG. 1 is a schematic illustration of a medical procedure using exampleinstrumentation of this disclosure.

FIG. 2 is a top view of one example catheter of this disclosure with aballoon in an expanded state, in use with a lasso catheter.

FIG. 3 is a perspective view of a multi-electrode ablation ballooncatheter along with the lasso catheter that can be used in the clinicalstudy.

FIG. 4A is an exploded perspective view of the yet another embodiment ofthe balloon ablation catheter from FIG. 3, which shows a base balloon orfirst expandable membrane with radiating electrode assemblies that arepartially covered by respective second and third expandable membranes;

FIG. 4B illustrates an embodiment of an assembled balloon ablationcatheter of FIG. 4A;

FIG. 5 is a side view of the balloon ablation catheter of FIG. 4B;

FIG. 6A is a blown-up side view of a portion of the membrane of FIG. 4A;

FIG. 6B illustrates a lateral or circumferential surface area notcovered by the hemispherical second and third expandable membranes ofFIG. 4B

FIG. 7 is a photograph of an actual prototype according to an embodimentdescribed and illustrated herein.

FIG. 8 is a photograph of yet another prototype of the embodimentsdescribed and illustrated herein.

FIG. 9 is a side view of a distal end of the catheter of FIG. 2 deployedin the region of a pulmonary vein and its ostium.

FIG. 10 is a top plan view of an example diagnostic catheter of thepresent disclosure.

FIG. 11 is a detailed view of a distal assembly of the diagnosticcatheter of FIG. 10.

FIG. 12 is a schematic sectional view of a heart showing insertion of adiagnostic catheter according to FIGS. 10 and 11 and into the leftatrium.

FIG. 13 shows a schematic overview of the study of this disclosure.

FIG. 14 shows a table summarizing recommended RF Energy DeliveryParameters in one example.

FIG. 15 shows a table summarizing intensity or severity of each AEassessed according to classifications.

FIG. 16 shows a table illustrating classifications based on AAD therapyadministered in the blanking and post-blanking periods in an examplestudy.

FIG. 17 depicts a graphical overview of one method or use according tothis disclosure.

FIG. 18 depicts a graphical overview of one method or use according tothis disclosure.

FIG. 19 depicts a graphical overview of one method or use according tothis disclosure.

FIG. 20 depicts a graphical overview of one method or use according tothis disclosure.

FIG. 21 depicts a graphical overview of one method or use according tothis disclosure.

FIG. 22 depicts a graphical overview of one method or use according tothis disclosure.

FIG. 23 depicts a graphical overview of one method or use according tothis disclosure.

FIG. 24 shows a table summarizing single shot isolation versusnon-isolation according to the study of this disclosure.

FIG. 25 shows a graph summarizing initial impedance according to thestudy of this disclosure.

FIG. 26 shows a graph summarizing temperature rise according to thestudy of this disclosure.

FIG. 27 shows a graph summarizing impedance drop according to the studyof this disclosure.

FIG. 28 shows a graph summarizing maximum temperature according to thestudy of this disclosure.

FIG. 29A shows a graph summarizing initial impedance variation among1-circle electrodes in the study of this disclosure.

FIG. 29B shows a table summarizing initial impedance variation among1-circle electrodes in the study of this disclosure.

FIG. 30 shows a graph summarizing single-shot PVI rate in the study ofthis disclosure.

FIG. 31 shows a graph summarizing time to isolation in the study of thisdisclosure.

FIG. 32 shows a graph summarizing inflation index in the study of thisdisclosure.

FIG. 33 shows a table summarizing predictors associated withcorresponding Pearson correlation and binary logistic regression valuesin the study of this disclosure with pre- and post-ablation parameters.

FIG. 34 shows a table summarizing predictors associated withcorresponding Pearson correlation and binary logistic regression valuesin the study of this disclosure with pre-ablation parameters.

FIG. 35 shows a table summarizing predictors associated withcorresponding Pearson correlation and binary logistic regression valuesin the study of this disclosure with post-ablation parameters.

FIG. 36 shows a table summarizing rankings of pre- and post-ablationparameters that were single shot predictors observed in the study ofthis disclosure.

FIG. 37 shows a graph summarizing correlations between mean initialimpedance and age of patients in the study of this disclosure.

FIG. 38 shows a graph summarizing correlations between mean initialimpedance and body mass index (BMI) of patients in the study of thisdisclosure.

FIG. 39 shows a graph summarizing correlations between initialtemperature and temperature rise in the study of this disclosure.

FIG. 40 shows a graph summarizing correlations between initialtemperature and temperature slope in the study of this disclosure.

FIG. 41 shows a graph summarizing correlations between initialtemperature and initial impedance in the study of this disclosure.

FIG. 42 shows a graph summarizing correlations between initialtemperature and impedance drop in the study of this disclosure.

FIG. 43 shows a graph summarizing correlations between initialtemperature variation and highest initial temperature in the study ofthis disclosure.

FIG. 44 shows a graph summarizing correlations between initialtemperature variation and impedance drop variation in the study of thisdisclosure.

FIG. 45 shows a graph summarizing correlations between initialtemperature variation and temperature rise variation in the study ofthis disclosure.

FIG. 46 shows a graph summarizing correlations between initialtemperature variation and temperature slope variation in the study ofthis disclosure.

FIG. 47 shows a graph summarizing correlations between initial impedanceand temperature rise in the study of this disclosure.

FIG. 48 shows a graph summarizing correlations between initial impedanceand temperature slope in the study of this disclosure.

FIG. 49 shows a graph summarizing correlations between initial impedanceand impedance drop in the study of this disclosure.

FIG. 50 shows a graph summarizing correlations between initial impedanceand impedance drop percent in the study of this disclosure.

FIG. 51 shows a graph summarizing correlations between initial impedancevariation and initial temperature variation in the study of thisdisclosure.

FIG. 52 shows a graph summarizing correlations between initial impedancevariation and impedance drop variation in the study of this disclosure.

FIG. 53 shows a graph summarizing correlations between initial impedancevariation and highest initial impedance in the study of this disclosure.

FIG. 54 shows a graph summarizing correlations between initial impedancevariation and mean initial impedance in the study of this disclosure.

FIG. 55 shows a graph summarizing correlations between initial impedancevariation and lowest impedance drop in the study of this disclosure.

FIG. 56 shows a graph summarizing correlations between lowesttemperature rise and lowest impedance drop in the study of thisdisclosure.

FIG. 57 shows a graph summarizing correlations between lowest impedancedrop and lowest temperature slope in the study of this disclosure.

FIG. 58 shows a graph summarizing correlations between lowesttemperature rise and lowest temperature slope in the study of thisdisclosure.

FIG. 59 shows a schematic summarizing correlative data sets forsingle-shot isolation predictors according to the study of thisdisclosure.

FIG. 60 shows a schematic summarizing correlative data sets forsingle-shot isolation evaluators according to the study of thisdisclosure.

FIG. 61A shows a computer simulation model executing one examplepredictor function.

FIG. 61B shows a table summarizing data associated with the simulationof FIG. 61A.

FIG. 61C shows a table summarizing data associated with the simulationof FIG. 61A.

FIG. 62A shows a computer simulation model executing one examplepredictor function.

FIG. 62B shows a table summarizing data associated with the simulationof FIG. 62A.

FIG. 62C shows a table summarizing data associated with the simulationof FIG. 62A.

FIG. 63A shows a computer simulation model executing one examplepredictor function.

FIG. 63B shows a table summarizing data associated with the simulationof FIG. 63A.

FIG. 63C shows a table summarizing data associated with the simulationof FIG. 63A.

FIG. 64A shows a computer simulation model executing one examplepredictor function.

FIG. 64B shows a table summarizing data associated with the simulationof FIG. 64A.

FIG. 64C shows a table summarizing data associated with the simulationof FIG. 64A.

FIG. 65A shows a computer simulation model executing one examplepredictor function.

FIG. 65B shows a table summarizing data associated with the simulationof FIG. 65A.

FIG. 65C shows a table summarizing data associated with the simulationof FIG. 65A.

FIG. 66A shows a computer simulation model executing one examplepredictor function.

FIG. 66B shows a table summarizing data associated with the simulationof FIG. 66A.

FIG. 66C shows a table summarizing data associated with the simulationof FIG. 66A.

FIG. 67 shows a table summarizing data associated with anothersimulation.

FIG. 68A shows a computer simulation model executing one exampleevaluator function.

FIG. 68B shows a table summarizing data associated with the simulationof FIG. 68A.

FIG. 68C shows a table summarizing data associated with the simulationof FIG. 68A.

FIG. 69A shows a computer simulation model executing one exampleevaluator function.

FIG. 69B shows a table summarizing data associated with the simulationof FIG. 69A.

FIG. 69C shows a table summarizing data associated with the simulationof FIG. 69A.

FIG. 70A shows a table summarizing data associated with a simulation ofan example evaluator algorithm.

FIG. 70B shows a table summarizing data associated with the simulationof the example evaluator algorithm of FIG. 70A.

FIG. 71A shows a computer simulation model executing one exampleevaluator function.

FIG. 71B shows a table summarizing data associated with the simulationof FIG. 71A.

FIG. 71C shows a table summarizing data associated with the simulationof FIG. 71A.

FIG. 72A shows a computer simulation model executing one exampleevaluator function.

FIG. 72B shows a table summarizing data associated with a simulation ofan example evaluator algorithm.

FIG. 72C shows a table summarizing data associated with a simulation ofan example evaluator algorithm.

FIG. 73A shows a table summarizing data associated with a simulation ofan example evaluator algorithm.

FIG. 73B shows a table summarizing data associated with a simulation ofan example evaluator algorithm.

FIG. 74 shows a table summarizing data associated with a simulation ofan example evaluator algorithm.

FIG. 75A shows a bar graph summarizing single shot isolation probabilityversus pre-ablation mean initial temperature in the study of thisdisclosure.

FIG. 75B shows a binary fitted line plot of single shot isolationprobability versus pre-ablation mean initial temperature in the study ofthis disclosure.

FIG. 76A shows a bar graph summarizing single shot isolation probabilityversus pre-ablation lowest initial temperature in the study of thisdisclosure.

FIG. 76B shows a binary fitted line plot of single shot isolationprobability versus pre-ablation lowest initial temperature in the studyof this disclosure.

FIG. 77A shows a bar graph summarizing single shot isolation probabilityversus pre-ablation highest initial temperature in the study of thisdisclosure.

FIG. 77B shows a binary fitted line plot of single shot isolationprobability versus pre-ablation highest initial temperature in the studyof this disclosure.

FIG. 78A shows a bar graph summarizing single shot isolation probabilityversus pre-ablation initial temperature variation in the study of thisdisclosure.

FIG. 78B shows a binary fitted line plot of single shot isolationprobability versus pre-ablation initial temperature variation in thestudy of this disclosure.

FIG. 79A shows a bar graph summarizing single shot isolation probabilityversus pre-ablation distributed initial temperature in the study of thisdisclosure.

FIG. 79B shows a binary fitted line plot of single shot isolationprobability versus pre-ablation distributed initial temperature in thestudy of this disclosure.

FIG. 80A shows a bar graph summarizing single shot isolation probabilityversus pre-ablation distributed initial temperature in the study of thisdisclosure.

FIG. 80B shows a binary fitted line plot of single shot isolationprobability versus pre-ablation distributed initial temperature in thestudy of this disclosure.

FIG. 81A shows a bar graph summarizing single shot isolation probabilityversus pre-ablation distributed initial temperature in the study of thisdisclosure.

FIG. 81B shows a binary fitted line plot of single shot isolationprobability versus pre-ablation distributed initial temperature in thestudy of this disclosure.

FIG. 82A shows a bar graph summarizing single shot isolation probabilityversus pre-ablation mean initial impedance in the study of thisdisclosure.

FIG. 82B shows a binary fitted line plot of single shot isolationprobability versus pre-ablation mean initial impedance in the study ofthis disclosure.

FIG. 83A shows a bar graph summarizing single shot isolation probabilityversus pre-ablation lowest initial impedance in the study of thisdisclosure.

FIG. 83B shows a binary fitted line plot of single shot isolationprobability versus pre-ablation lowest initial impedance in the study ofthis disclosure.

FIG. 84A shows a bar graph summarizing single shot isolation probabilityversus pre-ablation highest initial impedance in the study of thisdisclosure.

FIG. 84B shows a binary fitted line plot of single shot isolationprobability versus pre-ablation highest initial impedance in the studyof this disclosure.

FIG. 85A shows a bar graph summarizing single shot isolation probabilityversus pre-ablation initial impedance variation in the study of thisdisclosure.

FIG. 85B shows a binary fitted line plot of single shot isolationprobability versus pre-ablation initial impedance variation in the studyof this disclosure.

FIG. 86A shows a bar graph summarizing single shot isolation probabilityversus pre-ablation initial anterior wall impedance in the study of thisdisclosure.

FIG. 86B shows a binary fitted line plot of single shot isolationprobability versus pre-ablation initial anterior wall impedance in thestudy of this disclosure.

FIG. 87A shows a bar graph summarizing single shot isolation probabilityversus pre-ablation lowest initial anterior wall impedance in the studyof this disclosure.

FIG. 87B shows a binary fitted line plot of single shot isolationprobability versus pre-ablation lowest initial anterior wall impedancein the study of this disclosure.

FIG. 88A shows a bar graph summarizing single shot isolation probabilityversus pre-ablation highest initial anterior wall impedance in the studyof this disclosure.

FIG. 88B shows a binary fitted line plot of single shot isolationprobability versus pre-ablation highest initial anterior wall impedancein the study of this disclosure.

FIG. 89A shows a bar graph summarizing single shot isolation probabilityversus pre-ablation initial anterior wall impedance variation in thestudy of this disclosure.

FIG. 89B shows a binary fitted line plot of single shot isolationprobability versus pre-ablation initial anterior wall impedancevariation in the study of this disclosure.

FIG. 90A shows a bar graph summarizing single shot isolation probabilityversus pre-ablation mean temperature slope in the study of thisdisclosure.

FIG. 90B shows a binary fitted line plot of single shot isolationprobability versus pre-ablation mean temperature slope in the study ofthis disclosure.

FIG. 91A shows a bar graph summarizing single shot isolation probabilityversus pre-ablation lowest temperature slope in the study of thisdisclosure.

FIG. 91B shows a binary fitted line plot of single shot isolationprobability versus pre-ablation lowest temperature slope in the study ofthis disclosure.

FIG. 92A shows a bar graph summarizing single shot isolation probabilityversus pre-ablation highest temperature slope in the study of thisdisclosure.

FIG. 92B shows a binary fitted line plot of single shot isolationprobability versus pre-ablation highest temperature slope in the studyof this disclosure.

FIG. 93A shows a bar graph summarizing single shot isolation probabilityversus pre-ablation temperature slope variation in the study of thisdisclosure.

FIG. 93B shows a binary fitted line plot of single shot isolationprobability versus pre-ablation temperature slope variation in the studyof this disclosure.

FIG. 94A shows a bar graph summarizing single shot isolation probabilityversus pre-ablation mean temperature rise in the study of thisdisclosure.

FIG. 94B shows a binary fitted line plot of single shot isolationprobability versus pre-ablation mean temperature rise in the study ofthis disclosure.

FIG. 95A shows a bar graph summarizing single shot isolation probabilityversus pre-ablation lowest value temperature rise in the study of thisdisclosure.

FIG. 95B shows a binary fitted line plot of single shot isolationprobability versus pre-ablation lowest value temperature rise in thestudy of this disclosure.

FIG. 96A shows a bar graph summarizing single shot isolation probabilityversus pre-ablation highest value temperature rise in the study of thisdisclosure.

FIG. 96B shows a binary fitted line plot of single shot isolationprobability versus pre-ablation highest value temperature rise in thestudy of this disclosure.

FIG. 97A shows a bar graph summarizing single shot isolation probabilityversus pre-ablation temperature rise variation in the study of thisdisclosure.

FIG. 97B shows a binary fitted line plot of single shot isolationprobability versus pre-ablation temperature rise variation in the studyof this disclosure.

FIG. 98A shows a bar graph summarizing single shot isolation probabilityversus pre-ablation maximum mean temperature in the study of thisdisclosure.

FIG. 98B shows a binary fitted line plot of single shot isolationprobability versus pre-ablation maximum mean temperature in the study ofthis disclosure.

FIG. 99A shows a bar graph summarizing single shot isolation probabilityversus pre-ablation lowest value maximum temperature in the study ofthis disclosure.

FIG. 99B shows a binary fitted line plot of single shot isolationprobability versus pre-ablation lowest value maximum temperature in thestudy of this disclosure.

FIG. 100A shows a bar graph summarizing single shot isolationprobability versus pre-ablation highest value maximum temperature in thestudy of this disclosure.

FIG. 100B shows a binary fitted line plot of single shot isolationprobability versus pre-ablation highest value maximum temperature in thestudy of this disclosure.

FIG. 101A shows a bar graph summarizing single shot isolationprobability versus pre-ablation maximum temperature variation in thestudy of this disclosure.

FIG. 101B shows a binary fitted line plot of single shot isolationprobability versus pre-ablation maximum temperature variation in thestudy of this disclosure.

FIG. 102A shows a bar graph summarizing single shot isolationprobability versus pre-ablation mean impedance drop in the study of thisdisclosure.

FIG. 102B shows a binary fitted line plot of single shot isolationprobability versus pre-ablation mean impedance drop in the study of thisdisclosure.

FIG. 103A shows a bar graph summarizing single shot isolationprobability versus pre-ablation lowest value impedance drop in the studyof this disclosure.

FIG. 103B shows a binary fitted line plot of single shot isolationprobability versus pre-ablation lowest value impedance drop in the studyof this disclosure.

FIG. 104A shows a bar graph summarizing single shot isolationprobability versus pre-ablation highest value impedance drop in thestudy of this disclosure.

FIG. 104B shows a binary fitted line plot of single shot isolationprobability versus pre-ablation highest value impedance drop in thestudy of this disclosure.

FIG. 105A shows a bar graph summarizing single shot isolationprobability versus pre-ablation impedance drop variation in the study ofthis disclosure.

FIG. 105B shows a binary fitted line plot of single shot isolationprobability versus pre-ablation impedance drop variation in the study ofthis disclosure.

FIG. 106A shows a bar graph summarizing single shot isolationprobability versus pre-ablation lowest value impedance drop percent inthe study of this disclosure.

FIG. 106B shows a binary fitted line plot of single shot isolationprobability versus pre-ablation lowest value impedance drop percent inthe study of this disclosure.

FIG. 107A shows a bar graph summarizing single shot isolationprobability versus pre-ablation impedance drop percent variation in thestudy of this disclosure.

FIG. 107B shows a binary fitted line plot of single shot isolationprobability versus pre-ablation impedance drop percent variation in thestudy of this disclosure.

FIG. 108A shows a bar graph summarizing single shot isolationprobability versus pre-ablation initial impedance deviation from meanvalue in the study of this disclosure.

FIG. 108B shows a binary fitted line plot of single shot isolationprobability versus pre-ablation initial impedance deviation from meanvalue in the study of this disclosure.

FIG. 109 shows a table summarizing predictors associated withcorresponding Pearson correlation and binary logistic regression valuesin the study of this disclosure.

FIG. 110 shows a table summarizing pre- and post-ablation parameters inthe study of this disclosure.

FIG. 111 shows a binary fitted line plot of probability of single shotisolation versus pre-ablation lowest anterior impedance in the study ofthis disclosure.

FIG. 112 shows a binary fitted line plot of probability of single shotisolation versus pre-ablation anterior impedance variation in the studyof this disclosure.

FIG. 113 shows a binary fitted line plot of probability of single shotisolation versus pre-ablation lowest impedance in the study of thisdisclosure.

FIG. 114 shows a binary fitted line plot of probability of single shotisolation versus pre-ablation mean impedance in the study of thisdisclosure.

FIG. 115 shows a binary fitted line plot of probability of single shotisolation versus pre-ablation impedance variation in the study of thisdisclosure.

FIG. 116 shows a binary fitted line plot of probability of single shotisolation versus post-ablation lowest maximum temperature in the studyof this disclosure.

FIG. 117 shows a binary fitted line plot of probability of single shotisolation versus post-ablation lowest impedance drop in the study ofthis disclosure.

FIG. 118 shows a binary fitted line plot of probability of single shotisolation versus post-ablation mean impedance drop in the study of thisdisclosure.

FIG. 119 shows a binary fitted line plot of probability of single shotisolation versus post-ablation impedance drop variation in the study ofthis disclosure.

FIG. 120A shows a graph summarizing electrode temperature versus time inthe study of this disclosure.

FIG. 120B shows a graph summarizing electrode impedance versus time inthe study of this disclosure.

FIG. 121 shows a table summarizing impedance and temperature values fromsingle shot information from the graphs of FIGS. 120A-120B

FIG. 122 shows a table demonstrating temperature and impedance trends inelectrodes of the balloon catheter as to single shot versusnon-isolation comparison for cases of the study of this disclosure.

FIG. 123A shows a graph summarizing electrode temperature versus time inthe study of this disclosure.

FIG. 123B shows a graph summarizing electrode impedance versus time inthe study of this disclosure.

FIG. 124 shows a graph summarizing electrode impedance phase versus timein the study of this disclosure.

FIG. 125 depicts a graphical overview of one method or use according tothis disclosure.

FIG. 126 depicts a graphical overview of one method or use according tothis disclosure.

FIG. 127 illustrates an exemplary flow chart of the subroutine todetermine a probability of success.

FIG. 128 shows an example graphical display representing acharacteristic and the identity of the electrodes energized during anexample ablation.

DETAILED DESCRIPTION

Although example embodiments of the disclosed technology are explainedin detail herein, it is to be understood that other embodiments areintended to be within the scope of the claimed invention. Accordingly,it is not intended that the disclosed technology be limited in its scopeto the details of construction and arrangement of components set forthin the following description or illustrated in the drawings. Thedisclosed technology is capable of other embodiments and of beingpracticed or carried out in various ways.

It must also be noted that, as used in the specification and theappended claims, the singular forms “a,” “an” and “the” include pluralreferents unless the context clearly dictates otherwise. By “comprising”or “containing” or “including” it is meant that at least the namedcompound, element, particle, or method or use step is present in thecomposition or article or method or use, but does not exclude thepresence of other compounds, materials, particles, method or use steps,even if the other such compounds, material, particles, method or usesteps have the same function as what is named.

As used herein, the terms “about” or “approximately” for any numericalvalues or ranges indicate a suitable dimensional tolerance that allowsthe part or collection of components to function for its intendedpurpose as described herein. More specifically, “about” or“approximately” can refer to the range of values ±20% of the recitedvalue, e.g. “about 90%” can refer to the range of values from 71% to99%.

In addition, as used herein, the terms “patient,” “host,” “user,” and“subject” refer to any human or animal subject and are not intended tolimit the systems or method or uses to human use, although use of thesubject invention in a human patient represents a preferred embodiment.

In describing example embodiments, terminology will be resorted to forthe sake of clarity. It is intended that each term contemplates itsbroadest meaning as understood by those skilled in the art and includesall technical equivalents that operate in a similar manner to accomplisha similar purpose. It is also to be understood that the mention of oneor more steps of a method or use does not preclude the presence ofadditional method or use steps or intervening method or use stepsbetween those steps expressly identified. Steps of a method or use canbe performed in a different order than those described herein withoutdeparting from the scope of the disclosed technology. Similarly, it isalso to be understood that the mention of one or more components in adevice or system does not preclude the presence of additional componentsor intervening components between those components expressly identified.

As discussed herein, vasculature of a “subject” or “patient” can bevasculature of a human or any animal. It should be appreciated that ananimal can be a variety of any applicable type, including, but notlimited thereto, mammal, veterinarian animal, livestock animal or pettype animal, etc. As an example, the animal can be a laboratory animalspecifically selected to have certain characteristics similar to a human(e.g., rat, dog, pig, monkey, or the like). It should be appreciatedthat the subject can be any applicable human patient, for example.

As discussed herein, “operator” can include a doctor, surgeon, or anyother individual or delivery instrumentation associated with delivery ofa multi-electrode RF balloon catheter for the treatment of drugrefractory atrial fibrillation to a subject.

As discussed herein, “NIHSS Score” means The National Institutes ofHealth Stroke Scale, or NIH Stroke Scale (NIHSS) and is a tool used byhealthcare providers to objectively quantify the impairment caused by astroke. The NIHSS is composed of 11 items, each of which scores aspecific ability between a 0 and 4. For each item, a score of 0typically indicates normal function in that specific ability, while ahigher score is indicative of some level of impairment. The individualscores from each item are summed in order to calculate a patient's totalNIHSS score. The maximum possible score is 42, with the minimum scorebeing a 0.

As discussed herein, “mRS” means the modified Rankin Scale (mRS) that isa commonly used scale for measuring the degree of disability ordependence in the daily activities of people who have suffered a strokeor other causes of neurological disability. The mRS scale runs from 0-6,running from perfect health without symptoms to death. An mRS score of 0is understood as no symptoms being observed. An mRS score of 1 isunderstood as no significant disability is observed and the patient isable to carry out all usual activities, despite some symptoms. An mRSscore of 2 is understood as slight disability and the patient is able tolook after own affairs without assistance, but unable to carry out allprevious activities. An mRS score of 3 is understood as moderatedisability whereby the patient can require some help but is able to walkunassisted. An mRS score of 4 is understood as moderate severedisability and the patient is unable to attend to own bodily needswithout assistance or walk unassisted. An mRS score of 5 is understoodas severe disability and the patient requires constant nursing care andattention, bedridden, incontinent. An mRS score of 6 is understood asthe patient being deceased.

As discussed herein, the term “safety”, as it relates to devices used inablating cardiac tissue, related delivery systems, or method or use oftreatment refers to a relatively low severity of adverse events,including adverse bleeding events, infusion or hypersensitivityreactions. Adverse bleeding events can be the primary safety endpointand include, for example, major bleeding, minor bleeding, and theindividual components of the composite endpoint of any bleeding event.

As discussed herein, unless otherwise noted, the term “clinicallyeffective” (used independently or to modify the term “effective”) canmean that it has been proven by a clinical trial wherein the clinicaltrial has met the approval standards of U.S. Food and DrugAdministration, EMEA or a corresponding national regulatory agency. Forexample, a clinical study can be an adequately sized, randomized,double-blinded controlled study used to clinically prove the effects ofthe cardiac ablation device(s) and related system(s) of this disclosure.Most preferably to clinically prove the effects of the device(s) withrespect to all targeted pulmonary veins, for example, to achieve aclinically effective outcome in for the patient (e.g., mRS less than orequal to 2) and/or achieve pulmonary vein isolation in those afflictedveins.

As discussed herein, the term “computed tomography” or CT means one ormore scans that make use of computer-processed combinations of manyX-ray measurements taken from different angles to producecross-sectional (tomographic) images (virtual “slices”) of specificareas of a scanned object, allowing the user to see inside the objectwithout cutting. Such CT scans of this disclosure can refer to X-ray CTas well as many other types of CT, such as positron emission tomography(PET) and single-photon emission computed tomography (SPECT).

The present disclosure is related to systems, method or uses and devicesfor ablating cardiac tissue to treat cardiac arrhythmias. Ablativeenergies are typically provided to cardiac tissue by a tip portion whichcan deliver ablative energy alongside the tissue to be ablated. Some ofthese catheters administer ablative energy from various electrodesthree-dimensional structures. Ablative procedures incorporating suchcatheters can be visualized using fluoroscopy.

Ablation of cardiac tissue to correct a malfunctioning heart is awell-known procedure. Typically, to successfully ablate, cardiacelectropotentials need to be measured at various locations of themyocardium. In addition, temperature measurements during ablationprovide data enabling the efficacy of the ablation to be measured.Typically, for an ablation procedure, the electropotentials and thetemperatures are measured before, during, and after the actual ablation.

Previous solutions have used two or more separate instructions (e.g.,one for the electropotentials and temperature measurements, and anotherfor the ablation), embodiments disclosed herein facilitate the twomeasurements, and in addition enable ablation using radiofrequencyelectromagnetic energy, using a single catheter. The catheter has alumen, and a balloon is deployed through the catheter lumen (the balloontravels through the lumen in a collapsed, uninflated configuration, andthe balloon is inflated on exiting the lumen). The balloon has anexterior wall or membrane and has a distal end and a proximal end whichdefine a longitudinal axis that extends the lumen.

As an example, FIG. 1 depicts example instrumentations that include anapparatus 12, according to an example embodiment. The procedure isperformed by an operator 14, and the procedure in the descriptionhereinbelow is assumed to comprise ablation of a portion of a myocardium16 of the heart of a human patient 18. However, it is understood thatembodiments disclosed herein are not merely applicable to this specificprocedure and can include substantially any procedure on biologicaltissue or on non-biological materials.

To perform the ablation, the operator 14 inserts a probe 20 into asheath 21 that has been pre-positioned in a lumen of the patient. Sheath21 is positioned so that a distal end 22 of probe 20 enters the heart ofthe patient. A multi-electrode radiofrequency balloon catheter 24 (e.g.,a balloon catheter), which is described in more detail below, isdeployed through a lumen 23 of the probe 20 and exits from a distal endof the probe 20. Catheter 24 can be a multi-electrode radiofrequencyballoon catheter for cardiac electrophysiological ablation of pulmonaryveins of the atria and, when used with a multi-channel RF generator, forthe treatment of drug refractory recurrent symptomatic PAF, as discussedmore particularly below. Catheter 24 and variations or updates tocatheter 24 can be understood as including features more clearlydescribed in Appendix 1 as incorporated by reference in its entiretyfrom the U.S. Provisional applications from which this applicationclaims priority, which includes U.S. Pat. Nos. 9,907,610; 9,956,035;U.S. Pat. Pubs. 2015/0272667; 2016/0175041; 2017/0311893; 2017/0311829;2017/0312022A1; 2018/0280080A1 (Ser. No. 15/476,191); 2018/0161093;2019/0183567 (Ser. No. 15/847,661); 2019/0175262; 2019/0060622 (Ser. No.15/684,434); 2019/0217065 (Ser. No. 15/870,375); 2019/0143079 (Ser. No.15/815,394); 2017/0347896; 2016/0175041 each of which are incorporatedby reference in their entirety as if set forth verbatim herein. Notethat such catheters 24 can be introduced through the femoral artery,wrist artery (radial access) or directly through the carotid artery.While both radial and carotid access avoids the aortic arches, there areother drawbacks. However, all three approaches are considered to beknown to ones of skill in this art.

Functionally, catheter 24 seeks to achieve isolation of the pulmonaryveins in the subject's LA to eliminate symptoms of AF. The catheter 24ablates from multiple irrigated, independently-controlled electrodessimultaneously. The amount of power delivered to each electrode iscontrolled independently to improve safety and lesion quality.

One RF generator intended for use in this disclosure can be for cardiacablation applications to generate RF energy for delivery to a site inthe heart via compatible RF ablation catheters. The generator is capableof independently controlling the delivery of RF energy to electrodessimultaneously. The generator can include functions for controllingablation parameters at the ablation electrodes of the catheter. Ablationparameters, such as power, impedance, ablation duration, and temperatureare recorded and can be exported at the end of the procedure to a USBdevice. The generator is typically configured to measure and display amagnitude of a complex impedance (Z) at least intended to represent theimpedance of the patient's tissue proximate the ablation electrode. Tomake the impedance measurement, the generator uses each of the pluralityof electrodes (i.e., one lead through the catheter to each ablationelectrode) and one RF indifferent/dispersive return (i.e., one lead fromthe RF indifferent return going back to the generator)—a two terminalconfiguration for measurement for each electrode. With this set up, thegenerator generates small currents between each electrode and theindifferent electrode and measures the voltage created by the current tocalculate the impedance for each electrode. As configured in thissystem, the impedance of the tissue in contact with each of the tenelectrodes can be detected by the processor 46 and analyzed to provideindicators and guidance for the operator during or after a procedure.

As shown in FIGS. 1 to 2, apparatus 12 is controlled by a systemprocessor 46, which is in an operating console 15 of the apparatus.Console 15 comprises controls 49 which are used by professional 14 tocommunicate with the processor. During the procedure, the processor 46typically tracks a location and an orientation of the distal end 22 ofthe probe 20, using any method or use known in the art. For example,processor 46 can use a magnetic tracking method or use, wherein magnetictransmitters 25X, 25Y and 25Z external to the patient 18 generatesignals in coils positioned in the distal end of the probe 20. TheCARTO® system (available from Biosense Webster, Inc. of Irvine, Calif.)uses such a tracking method or use.

To operate apparatus 12, the processor 46 communicates with a memory 50,which has many modules used by the processor to operate the apparatus.Thus, the memory 50 comprises a temperature module 52, an ablationmodule 54, and an electrocardiograph (ECG) module 56, the functions ofwhich are described below. The memory 50 typically comprises othermodules, such as a force module for measuring the force on the distalend 22, a tracking module for operating the tracking method or use usedby the processor 46, and an irrigation module allowing the processor tocontrol irrigation provided for the distal end 22.

While other modules are not illustrated in FIG. 1, others are indeedintended to be within the scope of the claimed invention and can includehardware as well as software elements. For example, module 54 caninclude a radio-frequency generator with at least one output or outputchannel, e.g., ten outputs or ten output channels. Each of the outputscan be separately and selectively activated or deactivated by a switch.That is, each switch can be disposed between the signal generator and arespective output. Thus, a generator with ten outputs would include tenswitches. These outputs can each be individually coupled to electrodeson an ablation catheter, e.g., the ten electrodes 33 on balloon 80,described in further detail below. Electrodes 33 can be irrigated,flexible gold-plated electrodes bonded thereto and used to deliver RFenergy in a unipolar fashion to the tissue and sense temperature at eachelectrode. Electrodes 33 can be oriented circularly to achieve goodcircumferential contact with the ostia of the pulmonary veins. Thecatheter 24 can ablate cardiac tissue from the independently-controlledelectrodes simultaneously when paired with a Multi-Channel RF generatorand the amount of power delivered to each electrode is controlledindependently.

Such an electrical connection can be achieved by establishing anelectrical path between each output and each electrode. For example,each output can be connected to a corresponding electrode by one or morewires or suitable electrical connectors. Thus, in some embodiments, anelectrical path can include at least one wire. In some embodiments, theelectrical path can further include an electrical connector and at leasta second wire. Thus, electrodes 33 can be selectively activated anddeactivated with the switches to receive radiofrequency energyseparately from each of the other electrodes.

FIG. 2 illustrate catheter 24, which has a usable length ofapproximately 110 cm (though other dimensions are intended to be withinthe scope of the claimed invention as needed or required). Catheter 24can have three major sections: handle 42, shaft portion 82 and distaltip 22. The shaft 82 can measure 10.5 F (French) with a 13.5 F maximumouter diameter around the balloon 80 when the balloon is in its fullycollapsed state. The catheter 24 can have a high-torque shaft 82, with auni-directional braided deflectable tip section. The shaft allows theplane of the curved tip with balloon 80 to be rotated to facilitateaccurate positioning of the catheter tip 22 to the desired site (ostiaof the pulmonary veins). The compliance of the balloon 80 allows for itsflexible surface electrodes 33 to conform to the anatomy when pressedagainst the tissue.

The handle section 42 can incorporate a deflection thumb knob allowingfor unidirectional deflection, a balloon advancement mechanism, and aluer fitting for balloon inflation and irrigation. An additional luerfitting can be included and located proximally to the ejector and serveas an entry port for a guidewire as well as distal irrigation and/orcontrast injection. The catheter 24 can be used with an irrigation pumpto control irrigation to the balloon. Heparinized normal saline can bedelivered through the luer fitting of the handle 42.

FIG. 3 is a schematic perspective view of an example multi-electroderadiofrequency balloon catheter 24 in an expandable configuration in theform of a balloon in its expanded configuration, according to anembodiment used in the study. In a disclosed embodiment, where themulti-electrode radiofrequency balloon catheter 24 is used to ablate anostium 11 of a lumen, such as a pulmonary vein 13, the multi-electroderadiofrequency balloon catheter 24 is supported by a tubular shaft 70having a proximal shaft portion 82 and a distal shaft end 88. The shaft70 includes a hollow central tube 74, which permits a catheter to passtherethrough and past the distal shaft end 88. The catheter can be alasso catheter 72, as illustrated, or a diagnostic catheter (i.e., forrecording ECG signals on propagating through heart tissues). It is alsointended that the catheter can have a relatively small diameter (e.g., 3mm) through which a similarly small diameter catheter, such as a focallinear catheter or the like, could be used. The lasso catheter 72 can beinserted into the pulmonary vein to position the multi-electroderadiofrequency balloon catheter 24 correctly with respect to the ostiumprior to ablation of the ostium. The distal lasso portion of thecatheter 72 is typically formed of shape-memory retentive material suchas nitinol. It is understood that the multi-electrode radiofrequencyballoon catheter 24 can also be used with a linear or focal catheter 99(as shown in broken lines in FIG. 3) in the PV or elsewhere in theheart. Any catheter used in conjunction with the multi-electroderadiofrequency balloon catheter 24 can have features and functions,including, for example, pressure sensing, ablation, diagnostic, e.g.,navigation and pacing.

The balloon 80 of the multi-electrode radiofrequency balloon catheter 24can have an exterior wall or membrane 26 of a bio-compatible material,for example, formed from a plastic such as polyethylene terephthalate(PET), polyurethane or PEBAX®. The shaft 70 and the distal shaft end 88define a longitudinal axis 78 of the balloon 80. The balloon 80 isdeployed, in a collapsed configuration, via the lumen 23 of the probe20, and can be expanded after exiting from the distal end 22. Themembrane 26 of the balloon 80 is formed with irrigation pores orapertures 27 through which the fluid (e.g., saline) can exit from theinterior of the balloon 80 to outside the balloon for cooling the tissueablation site at the ostium. It is understood that the fluid can exitthe balloon 80 with any desired flow rate or pressure, including a ratewhere the fluid is seeping out of the balloon 80.

Yet another embodiment of the catheter can be utilized, referenced hereas probe 24′. FIG. 4A illustrates an exploded perspective view of theelectrophysiology probe 24′ that includes a tubular member 302 extendingalong a longitudinal axis L-L from a first (proximal) end 302 b to asecond (or distal) end 302 a. A first expandable membrane 204 isattached to the tubular member 302 near the distal end 302 b. Themembrane 204 has an outer surface 204 a and an inner surface 204 bdisposed about the longitudinal axis L-L. The outer surface 204 a isexposed to the ambient environment while the inner surface 204 b isexposed to the internal volume of the balloon defined by the membrane204. The first expandable membrane 204 has a first expandable distalmembrane portion 208 being coupled to the second end 302 a of thetubular member 302 and second expandable distal membrane portion 206spaced apart from the first expandable distal membrane portion 208 alongthe longitudinal axis L-L.

It is noted that first expandable membrane 204 is configured to beexpanded from a compressed shape (generally tubular configuration) to aballoon (or generally spheroidal) shaped member. A plurality ofelectrodes 210 a, 210 b, 210 c, 210 d, 210 e, 210 f, 210 g, 210 h, 210 iand 210 j, (which may be referred to singularly or collectively as“electrode 210”) are disposed on the outer surface 204 a of the firstexpandable membrane 204. The electrodes 210 are arranged so that theyradiate from a generally common center or centroid substrate 212 nearthe second expandable distal membrane portion 208 which is distal to thetubular member 302. The electrodes 210 a-210 j may have one or morewires, i.e., bifilar 214 a-214 j, respectively, connected to each of theplurality of electrodes 210 a-210 j via a connection junction 216 a-216j. Each of the wires 214 a-214 j (which may be singular in form “wire”or plural “wires” will be collectively referred to as “wire 214”) isconnected to the connection point at the “underside” surface of theelectrode 210. The underside surface of each electrode 210 is theelectrode surface that is not exposed to the ambient environment and istypically bonded to the outer surface 204 a of the membrane 204. As theconnection point 216 (typically a solder point) is generally at thecenter of the electrode, the wire is covered by the underside surface ofeach electrode. However, as each wire or bifilar 214 a-214 j extendstoward the tubular member 302, the electrode surface or the substrate onwhich the electrode is bonded thereto becomes smaller thereby leavingthe wire or bifilars 214 a-214 j exposed.

As can be seen in FIG. 4B, when group of wires 214 a-214 j are mountedon the membrane 204, each wire 214 is configured to extend from thetubular member 302 to the respective electrode 210 such that each wirefollows the topographic outer surface 204 a of membrane 204. Inextending the wires 214 toward the tubular member 302, the wires 214become exposed to the ambient environment (e.g., biological tissues orblood) as each wire 214 leaves the underside surface of each electrodeor the underside surface of the substrate 213 (FIG. 5). As each wire 214may be used to conduct or transmit electrical energy or signals, itwould be detrimental to expose the wires 214 to the ambient biologicaltissue environment. As such, we have devised a second expandablemembrane 200 that encapsulates the one or more wires (214 a-214 j)between the second expandable membrane 200 and the first expandablemembrane 204 so that the wires 214 a-214 j are constrained between thefirst and second expandable membrane (FIG. 7). Such configurationeliminates the exposure of the wires to the ambient environment yetstill allowing the electrodes/thermocouples to be exposed to biologicaltissues so that the electrodes and thermocouples to work for theirintended purposes. Moreover, as the wires 214 are constrained orcaptured between the first and second membranes, there is virtually nolikelihood of the wires being entangled or mis-connected to the wrongelectrode or thermocouple during assembly. In the preferred embodiment,each wire of the bifilar is coupled to a temperature sensor in the formof a thermocouple 216 disposed on or near each electrode 210.

It is noted that tubular member 302 defines a first internal passagewayin the form of a lumen 302 c, shown here as dashed lines in FIG. 5, thatextends from the first end 302 a to the second end 302 b of tubularmember 302 so that the one or more wires are disposed in the first lumen302 c. To allow other instruments (e.g., guide wires, optical sensoretc.,) to be delivered through the balloon 204 (and outside of thedistal-most portion 209 of balloon) the tubular member 302 can beprovided with a second lumen 302 d that extends through the membraneportions 206 and 208 to allow for another instrument to pass through thesecond lumen 302 d. Additionally, the tubular member 302 can be providedwith yet another internal passageway in the form of a third lumen 302 e.Irrigation fluid can be provided in either of the second lumen 302 d orthird lumen 302 e so that the irrigation fluid flows into the internalvolume of the membrane 204, through openings or pores 220 providedthrough the membrane inner surface 204 b and outer surface 204 a tooutside of the membrane 204 to the ambient environment (e.g., biologicaltissues or organ). Each electrode may have four irrigation openingsformed on the electrode such that the electrode irrigation openings arealigned with the pores 220 of the membrane. In the preferred embodiment,lumen 302 c, lumen 302 d and 302 e are configured or extruded asconcentric passageways, in the form of a tube 302 e within tube 302 dwithin a tube 302 c with outer tubular member 302. Tubular member 302can be a suitable biocompatible polymer as is known to those skilled inthe art.

Referring to FIG. 4B, the plurality of electrodes 210 a-210 j extendfrom a substrate centroid 212 equiangularly about the longitudinal axisL-L from the first expandable distal membrane portion 208 towards thesecond expandable distal membrane portion 206 such that the secondexpandable membrane 200 encapsulates a portion of each of the electrodes(210 a-210 j) proximate the second expandable membrane portion 206. Thesecond expandable membrane 200 has a border 202 (FIG. 4A) that extendsover a proximal portion (i.e., fish-head 115) of the electrode 210 outersurface (FIG. 4B) while allowing the electrode fish-bone pattern 210 tobe exposed to the ambient environment.

That is, each of the plurality of electrodes 210 a-210 j defines afishbone pattern not covered by the second expandable membrane 200 toallow the fishbone electrodes to be exposed to the ambient environment.Each electrode (210 a-210 j) is coupled to the outer surface of thefirst expandable membrane 204 via a substrate 213 which itself isconnected to or bonded to the outer surface 204 a of the firstexpandable membrane 204. The electrode 210 a-210 j can have a portion ofits perimeter bonded directly to membrane 204. A suitable seal 211 canbe formed so that the seal 211 runs along the outer perimeter of thesubstrate 213 of each electrode (210 a-210 j). In a preferredembodiment, the seal 211 can be provided in the form of a polyurethaneseal.

Referring to FIG. 5, a radiopaque marker 230 is defined by a proximalfish-head portion of each electrode such that there can be respectiveradiopaque markers 230 a, 230 b, 230 c, 230 d, 230 e, 230 f, 230 g, 230h, 230 i and 230 j for corresponding electrodes 210 a-210 j. To ensurethat the location of each electrode can be determined while inside abody organ with x-rays, each electrode 210 may have a radiopaque marker(230 a-230 j) with each marker having a configuration different fromother radiopaque markers on the other electrodes.

Referring back to FIG. 4A, a third expandable membrane 300 can bedisposed proximate the first expandable distal membrane portion 208 sothat the third expandable membrane 300 encircles an outer surfaceportion of the first expandable membrane 204 about the longitudinal axisL-L proximate the distal portion 209 of the membrane 204. The thirdexpandable membrane encapsulates a portion of the substrate 213 (FIG. 5)for each of the plurality of electrodes near distal portion 209 ofmembrane 204. Preferably, the third expandable membrane 300 allows forencapsulation of the substrates 213 of each electrode (210 a-210 j) asthe substrates 213 converge to centroid 212 near the distal portion 209of the membrane 204. A retaining ring 209 is disposed about the thirdexpandable membrane 300 (near distal portion 208 of membrane 204) tohold the third expandable membrane 300 as well as the substrates 213 tothe first expandable membrane 204. The third expandable membrane 300 canbe bonded to the first expandable membrane 204 thereby capturing thesubstrate 213 therebetween the two membranes (204 and 300).

Referring to FIG. 6A, a blown-up side view of a portion of the membraneof FIG. 4A is shown. FIG. 6B shows a lateral or circumferential surfacearea that is not covered. In particular, the surface area of themembrane 204 that is exposed (i.e., not covered) by second expandablemembrane 200 and third expandable membrane has a circumferential surfacearea L delineated between a virtual slice S1 (defined by theintersection of third expandable membrane 300 with first expandablemembrane 204) orthogonal to axis L-L and virtual slice S2 orthogonal tothe longitudinal axis L-L whereby slice S2 is defined by theintersection of the second expandable membrane 200 to the firstexpandable membrane 204. For clarity, it can be seen in FIG. 6B that ifthe first expandable membrane 204 approximates a sphere (when membrane204 is expanded to its service characteristic) then the circumferentialsurface area L can be determined once the parameters of the spheroidbody is known. In the preferred embodiment, shown in FIG. 7, the firstexpandable membrane 204 includes a circumferential surface area L (FIGS.5 and 6B) of approximately 52% of a total surface area of the firstexpandable membrane 204. That is, the circumferential surface area L isthe exposed surface area (without any electrode or substrate) of firstexpandable membrane 204 or outer circumferential area of firstexpandable membrane 204 that is also not covered by the secondexpandable membrane 200 and third expandable membrane 300. Further, itis noted that each substrate 213 for each electrode 210 includes asubstrate surface area approximately 8% of the exposed outercircumferential surface area L of the first expandable membrane 204. Inthe preferred embodiments, the second expandable membrane 200 and thirdexpandable membrane 300 cover approximately half of the outer surfacearea of the first expandable membrane 204.

In the preferred embodiments, the first expandable membrane includes agenerally spheroidal member with a diameter as referenced to thelongitudinal axis L-L of about 30 millimeters and the second expandablemembrane and the third expandable membrane each includes ahemi-spherical member with the respective major diameter of eachhemispherical member being less than 30 mm. In the preferredembodiments, the total surface area of membrane 204 is about 4500squared-mm while the circumferential surface area L is about 2400squared-mm and each flexible substrate 213 is about 200 squared-mm whenthe membrane 204 is at its fully expanded (i.e., designed)configuration, shown exemplarily in FIG. 7.

The balloon 204 of the diagnostic/therapeutic catheter has an exteriorwall or membrane 204 a of a bio-compatible material, for example, formedfrom a plastic such as polyethylene terephthalate (PET), polyurethane orPEBAX®. The tubular shaft 302 and the distal shaft end 302 a define alongitudinal axis L-L of the balloon 204. The balloon 204 is deployed,in a collapsed configuration as described in commonly-owned U.S. patentapplication Ser. No. 15/939,154 filed on Mar. 28, 2018 (via the lumen 23of the probe 20 in this prior application, which is incorporated byreference herein to this present application). The membrane 204 a of theballoon 204 is formed with irrigation pores or apertures 220 (shown inFIG. 5) through which the fluid (e.g., saline) can exit from theinterior of the balloon 204 to outside the balloon for cooling thetissue ablation site at the ostium.

As described earlier in relation to FIG. 4B, membrane 24 supports andcarries a combined electrode and temperature sensing member which isconstructed as a multi-layer flexible circuit electrode assembly 210a-210 j. The “flex circuit electrode assembly” 210 a-210 j may have manydifferent geometric configurations than as shown here. In theillustrated embodiment, the flex circuit electrode assembly 210 a-210 jhas a plurality of radiating substrates or strips 213 a-213 j, as bestseen in FIG. 2. The substrates 213 a-213 j are evenly distributed aboutthe distal end 209 and the balloon 204. Each substrate 213 a-213 j haswider proximal portion that gradually tapers to a narrower distalportion as referenced to the longitudinal axis.

For simplicity, the flex circuit electrode assembly 210 is describedwith respect to one of its substrate 213 as shown in FIG. 5, although itis understood that following description may apply to each substrate 213of the assembly 210. The flex circuit electrode assembly 210 includes aflexible and resilient sheet substrate material 213, constructed ofsuitable bio-compatible materials, for example, polyimide. In someembodiments, the sheet substrate material 213 has a greater heatresistance (or a higher melting temperature) compared to that of theballoon membrane 204. In some embodiments, the substrate material 213 isconstructed of a thermoset material having a decomposition temperaturethat is higher than the melting temperature of the balloon membrane 204by approximately 24 degrees Celsius or more.

The substrate material 213 is formed with one or more irrigation poresor apertures (not labeled) that are in alignment with the irrigationapertures 220 of the balloon member 204 so that fluid passing throughthe irrigation apertures 220 and (not labeled) can pass to the ablationsite on the ostium.

The substrate material 213 has a first or outer surface facing away fromthe balloon membrane 204, and a second or inner surface facing theballoon membrane 204. On its outer surface, the substrate material 213supports and carries the contact electrodes 210. The configuration ortrace of the contact electrode 210 may resemble a “fishbone” but itshould be noted that the invention is not limited to such configuration.In contrast to an area or “patch” ablation electrode, the fingers of thecontact electrode 210 advantageously increase the circumferential orequatorial contact surface of the contact electrode 210 with the ostiumwhile void regions between adjacent fingers advantageously allow theballoon 204 to collapse inwardly or expand radially as needed atlocations along its equator. In the illustrated embodiment, the fingershave different lengths, some being longer, others being shorter. Forexample, the plurality of fingers includes a distal finger, a proximalfinger and fingers therebetween, where each of the fingers in betweenhas a shorter adjacent finger. For example, each finger has a lengthdifferent from its distal or proximal immediately adjacent neighboringfinger(s) such that the length of each finger generally follows thetapered configuration of each substrate 213. In the illustratedembodiment, there are 22 fingers extending across (past each lateralside of) the elongated portion. In some embodiments, the contactelectrode 210 includes gold with a seed layer between the gold and themembrane 204. The seed layer may include titanium, tungsten, palladium,silver, or combinations thereof.

As shown in FIG. 8, the flexible electrode may have its radiopaquemarker in the variation identified as 231 a, 231 b, 231 c and so on toassist in the identification of the electrode being energized. Themarkers 231 a-231 j have various serpentine configurations (as comparedto FIG. 7) to allow for increased flexibility due to the presence of thesecond membrane 200 which tend to reduce the flexibility of the devicenear the markers 231 a-231 j.

FIG. 9 is a side view of a distal end of the catheter of FIG. 2 deployedin the region of a pulmonary vein and its ostium. FIG. 10 is a top planview of an example diagnostic catheter of the present disclosure. FIG.11 is a detailed view of a distal assembly of the diagnostic catheter ofFIG. 5.

The membrane 26 supports and carries a combined electrode andtemperature sensing member which is constructed as a multi-layerflexible circuit electrode assembly 84. The “flex circuit electrodeassembly” 84 can have many different geometric configurations. In theillustrated embodiment, the flex circuit electrode assembly 84 has aplurality of radiating substrates or strips 30. One or more electrodes33 on each substrate come into galvanic contract with the ostium 11during an ablation procedure, during which electrical current flows fromthe electrodes 33 to the ostium 11, as shown in FIG. 4.

The circuit which contains the electrodes 33 can be made of a veryflexible and resilient polyimide substrate (e.g., about0.001-inch-thick) with a layer of gold on the top (exterior surface) anda layer of gold-plated copper on the back side (between the circuit andthe balloon 80). In order to deliver current to the electrodes 33, abifilar wire can be connected to each electrode 33, routed through thecatheter 24, and terminated in the connector in the handle 42. Thebifilar wire can be made of one copper and one constantan wire. Thecopper wire can be used for RF delivery. In order to fit the catheter 24into the sheath, it is necessary to first collapse the balloon 80 withits flexible electrodes 33 to a smaller diameter by moving the distalend of the balloon 80 forward a specific distance to provide theelongation necessary to decrease the balloon's outer diameter (OD).

One example of diagnostic catheter 110 used in this disclosure is shownin FIGS. 10-11 and includes lasso-type structures to facilitatemaneuvering and positioning in the heart. Catheter 110 can be understoodas including features more clearly described in Appendix 2 asincorporated by reference in its entirety from the U.S. Provisionalapplications from which this application claims priority which includesU.S. Provisional Patent Application Ser. No. 62/769,424 (filed Nov. 19,2019); 62/692,439 (filed Jun. 29, 2018); U.S. Pat. Nos. 5,718,241;6,198,974; 6,484,118; 6,987,995; 7,142,903; 7,274,957; 7,377,906;7,591,799; 7,593,760; 7,720,517; 7,853,302; 8,000,765; 8,021,327;8,275,440; and 8,348,888, each of which are incorporated by reference intheir entirety as if set forth verbatim herein. Such catheters 110 canbe used to produce curved, circular, looped or otherwise closed ablationpaths, as well as sensing electrical activity along a curve, circle,loop or closed pattern for electrical potential and anatomical mapping.

Catheter 110 can therefore be an electrophysiological recording andstimulation of the atrial region of the heart and can be used inconjunction with catheter 24, as well as other ancillary equipment.Catheter 110's distal end can be a circular spine with ring electrodeslocated circularly and are used for stimulation and recording within theatria. The looped distal end is available in multiple diameters (15 mm,20 mm and 25 mm) to achieve an optimal contact in variably sizedpulmonary veins. In some examples, the loop tip can be a circular spinewith ten electrodes bonded to its surface, a straight distal tip sectionand a hypotube shaft. The ten electrodes can be used for stimulation andrecording within the atria of the heart and oriented circularly on theloop to achieve appropriate circumferential contact with the inside ofthe PV. Nominal electrode spacing can include 4.5 mm for the 15 mm loop,6 mm for the 20 mm loop, and 8 mm for the 25 mm loop.

Catheter 110 according to the disclosed example can include an elongatedbody that can include an insertion shaft or catheter body 112 having alongitudinal axis, and an intermediate section 114 distal of thecatheter body that can be uni- or bi-directionally deflected off axisfrom the catheter body longitudinal axis. A resilient three-dimensionaldistal assembly 117, with ring electrodes 119 disposed along a nonlinearor curved distal portion, extends from the elongated body 112 or theintermediate section 114. The helical form is oriented obliquelyrelative to a longitudinal axis 125 of the catheter 110 extending fromthe intermediate section 114. The term “obliquely”, in this respectmeans that the plane P in space that best fits the helical form isangled relative to the longitudinal axis 125. An angle θ between theplane P and the axis 125 ranges between about 45 to 105 degrees,preferably between about 75 to 105 degrees, and more preferably about 90degrees. Moreover, the helical form 122 of the distal assembly 117spirals or subtends in a predetermined manner.

The distal assembly 117 can have an electrode-carrying proximal loop117P, and a soft “pigtail” that includes a distal loop 117D and a distalstraight end section 117E, wherein the distal’ loop 117D and the distalstraight end section 117E have a greater resiliency than the resiliencyof the electrode-carrying proximal loop 117P. The pitch of the helicalform 122 of the distal assembly 117 is selected to provide a gentlepressure for ensuring contact of all of ring electrodes 119 with tissue.It is understood that tapering of the helical form 122 ensures that thesmaller distal loop 117D can fit into the tubular region or pulmonaryvein which ensures placement of accuracy of the larger proximal loop117P and the ring electrodes 119 carried thereon at an ostium 111 of thetubular region 113, e.g., a pulmonary vein. The greater flexibility ofthe distal loop 117D and the distal straight end section 117E providesan atraumatic leading element that guides distal assembly 117 into thetubular region or pulmonary vein and ensures placement accuracy of thedistal assembly.

The catheter 110 enters a patient's body through a guiding sheath thathas been inserted in a body cavity, such as a heart chamber. Due to theflexible construction of the distal assembly 117, the helical form 122readily straightens for insertion into the guiding sheath. When exposedand unconstrained, the distal assembly 117 reassumes the helical form122 which is maneuvered to engage the tissue surface frontally with someor all of the ring electrodes 119 on the proximal loop 117P contactingthe tissue surface simultaneously.

FIG. 12 is a schematic sectional view of heart 226, showing insertion ofcatheter 110 into the heart. To insert catheter 110, the user firstpasses a guiding sheath 240 percutaneously through the vascular systemand into right atrium 244 of the heart through ascending vena cava 242.The sheath penetrates through interatrial septum 248, typically via thefossa ovalis, into left atrium 246. Alternatively, other approach pathscan be used. Catheter 110 is then inserted through the guiding sheathuntil the distal assembly 117 of the catheter 110 extends past thedistal end of the guiding sheath 240 into the left atrium 246.

Continuing on with the procedure, the operator aligns the longitudinalaxis of guiding sheath 240 (and of catheter 110) inside left atrium 246with the axis of one of pulmonary veins. Alignment can be performedunder fluoroscopic or other means of visualization. The user advancesthe catheter 110 distally toward the pulmonary vein so that the softdistal end 117E first enters the pulmonary vein, followed by the softdistal loop 117D, both of which guide the positioning and placement ofthe electrode-carrying proximal loop 117P onto the ostium. The user canapply a force F in the axial direction to press the proximal loop 117Ponto the ostium to ensure contact between the ring electrodes 119 andthe tissue.

The operator can rotate the catheter 110 about its axis within theguiding sheath 240 so that the proximal loop 117P traces an annular patharound the inner circumference of the vein. Meanwhile, the user canactuate an RF generator to ablate the tissue in contact with the ARelectrodes along the path. Simultaneously, impedance and/or PV potentialrecordings can be made with the IR and/or RR electrodes. Aftercompleting this procedure around one pulmonary vein, the user can shiftthe sheath 240 and catheter 110 and repeat the procedure around one ormore of the other pulmonary veins.

Study Overview

This disclosure is more clearly understood with a corresponding studydiscussed more particularly below with respect to treatment of PAF. FIG.13 in particular provides a schematic overview of the subject studyprotocol of this disclosure as Appendix 3 and Appendix 4, each of whichare incorporated by reference in their entirety as if set forth verbatimherein. The purpose of this study is to prove that the use of thecatheter 24, as depicted graphically in FIG. 3, in conjunction with thecatheter 110, for the isolation of the atrial pulmonary veins intreatment of subjects with drug refractory, symptomatic, paroxysmalatrial fibrillation is clinically safe and clinically effective.

The study was a prospective, multicenter, single arm clinical evaluationutilizing catheters 24 and 110. The sample size for the study isprimarily driven by the safety endpoint. An adaptive Bayesian design canbe used to determine the sample size based on the safety endpoint alone.Sample size selection interim analyses can be performed when 80, 130,180, and 230 evaluable subjects are enrolled in the main study (e.g.,mITT Population). Safety outcome at 30 days will be used as a proxy forthe primary safety endpoint at each interim. The final safety analysisis on complete follow-up for the primary safety endpoint for allevaluable patients in the main study. Predictive probabilities ofsuccess are used to determine whether the sample size at each interimanalysis will be sufficient or if the trial enrollment will continue.Sample size simulations were performed using performance goals of 15%and 80% respectively for the safety and effectiveness endpoint rates.

At the time of each interim analysis, predictive probabilities ofsuccess are estimated using the available data from all evaluablesubjects in the mITT population, assuming a non-informative uniformprior distribution for the primary safety rate. Enrollment is stopped ifthe predictive probability of trial success at any interim is greaterthan 90%, or if the predictive probability of trial success with themaximum sample size is less than a futility bound of 6.5%. Otherwise,enrollment continues until the next interim or the final sample size.Analysis of the effectiveness endpoint is performed at the final samplesize determined for the safety endpoint. Power for the effectivenessendpoint assessment is >80% at all sample sizes N30 subjects.

The primary safety and effectiveness endpoints are evaluated using exacttests for binomial proportions at a one-sided 5% significance level.

In order to control for operational bias, the timing and results of theinterim analyses are not revealed to study investigators unless aninterim analysis results in a decision to stop enrollment. The interimanalyses are conducted seamlessly with no interruption to studyenrollment unless indicated by an interim analysis. The predictedprobability of study success or summary results which are calculated atthe time of the interim analysis is not disseminated by the statisticianperforming the interim analysis until the time of the final databaselock for the CSR.

Analyses for primary effectiveness endpoint included null andalternative hypotheses, including Ho: PE<0.80 and Ha: PE>0.80. It isunderstood that primary effectiveness (PE) can mean proportion ofpatients with acute procedural success defined as confirmation ofentrance block in treated PVs after adenosine and/or isoproterenolchallenge (with or without the use of a focal catheter). Theper-protocol population is used as the primary analysis population.Subjects with missing effectiveness endpoints data will be excluded inthe primary analysis. Sensitivity analyses for missing data is performedusing the PP and population to assess the impact of missing data on theprimary effectiveness outcome and are described in the StatisticalAnalysis Plan (SAP).

With respect ablation parameters of the study, electrodes 33 of catheter24 can make contact with the tissue due to the balloon 80 and length ofthe electrodes, which each helps in accommodating variable anatomy. Thepower needed to create a circumferential contiguous lesion in the ostiumto the pulmonary vein is therefore less than that of other RF catheters.Power delivery from each electrode is regulated by the generator and isdetermined by user input and by the temperature read by the thermocouplelocated on the electrode.

When used with the catheter 24, the irrigation pump of the studydelivered a continuous infusion of 5 mL/minute of room temperatureheparinized saline (1 u heparin/1 mL saline) when not delivering RFcurrent. To inflate the balloon and during ablation, the high flowsetting was used to deliver 35 mL/minute. The recommended operatingparameters for the catheter 24 are presented in FIG. 14.

The study duration is approximately 21 months for the enrollment phaseand follow-up. It is understood that data is presented herein forpurposes of illustration and should not be construed as limiting thescope of the disclosed technology in any way or excluding anyalternative or additional embodiments.

The study can demonstrate the clinical safety and acute effectiveness ofthe balloon catheter 24 when used with catheter 110 in the isolation ofthe atrial pulmonary veins in treatment of subjects with ParoxysmalAtrial Fibrillation (PAF). Specifically, the study can demonstrate theclinical safety based on the incidence of early-onset (within 7 days ofthe mapping and ablation procedure) primary adverse events (PAE). FIG.15 shows a table summarizing intensity or severity of each AE assessedaccording to classifications. For purposes of this disclosure, an AE canbe any undesirable experience (sign, symptom, illness, abnormallaboratory value, or other medical event) occurring to a subject duringthe course of the study, whether or not it is related to the device orprocedure. Physical findings (including vital signs) observed atfollow-up, or preexisting physical findings that worsen compared tobaseline, are adverse events if the investigator determines they areclinically significant. As to the study, any medical condition presentat the time that the subject is screened is considered as baseline andnot reported as an AE. Such conditions should be added to backgroundmedical history, if not previously reported. However, if the studysubject's condition deteriorates at any time during the study, it can berecorded as an AE. To demonstrate the acute and/or long-termeffectiveness based on the proportion of acute procedural success,whereby success in this context can be defined as confirmation ofentrance block in treated pulmonary veins after adenosine and/orisoproterenol challenge, including with or without the use of a focalablation catheter.

Subjects with drug symptomatic PAF were enrolled and the patientpopulation size included a maximum of 230 evaluable subjects (thoughfewer or more subjects could be investigated as needed or required,including populations such as 80, 130, and 180). Subjects can beevaluated prior to the procedure, prior to discharge, and post procedureat 7 days (4-10 days), 1 month (23-37 days), 3 months (76-104 days), and6 months (150-210 days).

The primary objective of study was demonstrating the clinical safety andacute effectiveness of catheter 24 in conjunction with catheter 110, inthe isolation of the atrial pulmonary veins in treatment of subjectswith paroxysmal atrial fibrillation. Specifically, the study sought todemonstrate the clinical safety based on the proportion of early-onsetprimary adverse events (within 7 days of ablation procedure) anddemonstrate the acute effectiveness based on the proportion of acuteprocedural success defined as confirmation of entrance block in treatedPVs after adenosine and/or isoproterenol challenge, including with orwithout the use of a focal ablation catheter.

Primary endpoints of the study include acute effectiveness and acutesafety. Acute safety can include incidence of early onset PrimaryAdverse Events (PAE) (within 7 days of an initial mapping and ablationprocedure which used one or more of the investigational devices).Throughout this disclosure, it is understood that an adverse event (AE)is any untoward medical occurrence in a subject whether or not relatedto the investigational medical device.

In contrast, the following clinical events were not considered anadverse event for this study: minor pericarditis attributable to theablation procedure defined as pleuritic chest discomfort with or withoutpericardial rub and ECG changes, AF/AFL/AT recurrence requiringpharmacological or synchronized electrical cardioversion during thehospitalization for the index ablation procedure, or throughout theduration of the study. However, new onset of left atrial flutteroccurring post-ablation is an AE, and re-ablation for AF or pre-existingAFL/AT itself is not an AE, however any procedural complication isconsidered an AE and shall be reported within the applicable timelines.

A serious adverse event (SAE) in this disclosure is any event that meetsone or more of the following criteria: leads to a death, leads to aserious deterioration in the health of a subject that resulted in alife-threatening illness or injury, a permanent impairment of a bodystructure or a body function, in-patient hospitalization or prolongationof an existing hospitalization, medical or surgical intervention toprevent life-threatening illness or injury or permanent impairment tobody structure or a body function, leads to fetal distress, fetal deathor a congenital abnormality or birth defect. It is understood thatplanned hospitalization for a condition present prior to the subject'senrollment in the study cannot meet the definition of an SAE. An AEwould meet the criterion of “hospitalization” if the event necessitatedan admission to a health care facility (e.g., an overnight stay).Emergency room visits that do not result in admission to the hospitalwere evaluated for one of the other serious outcomes. For furtherreference, FIG. 16 is provided summarizing classifications for theintensity or severity of each AE.

In the study, PAEs included the following AEs: device or procedurerelated death, Atrio-Esophageal Fistula, Myocardial Infarction, CardiacTamponade/Perforation, Thromboembolism, Stroke/Cerebrovascular Accident(CVA), Transient Ischemic Attach (TIA), Phrenic Nerve Paralysis,Pulmonary Vein Stenosis, Pericarditis, Pulmonary Edema, Major VascularAccess Complication/Bleeding, and Hospitalization (initial orprolonged). In the study, events were considered as primary AEs even ifthey occur greater than one week (7 days) post-procedure. Events relatedto hospitalization were excluded solely due to arrhythmia recurrence ornon-medically urgent cardioversion.

Secondary endpoints of the study as to safety included incidence ofindividual PAEs from the primary composite, incidence of Serious AdverseDevice Effects (SADEs), incidence of Serious Adverse Events (SAEs)within 7 days (early-onset), >7-30 days (peri-procedural), and >30 days(late onset) of initial ablation procedure, incidence of non-seriousadverse events, acute procedural success defined as confirmation ofentrance block in treated pulmonary veins (PVs) after adenosinechallenge (with or without the use of a focal catheter), pulmonary veinisolation (PVI) touch-up by focal catheter among all targeted veins andby subject during the index procedure, use of focal catheter ablationfor non-PV triggers during the index procedure, freedom from documentedAF/AT/Atypical (left-side) AFL episodes based on electrocardiographicdata through the effectiveness evaluation period (day 91-365 post indexprocedure) off Class I and III AADs, average number of RF applications,and RF time, required to isolate common pulmonary veins, incidence ofhospitalization for cardiovascular events (with hospitalization definedas prolonged stay ≥2 nights post standard index procedure or in-patientstay not concurrent with index procedure ≥1 calendar day), HealthEconomics data including but not limited to index procedure workflowcosts, quality of life (QoL), and hospital cost, incidence ofpre-procedure and post-ablation asymptomatic and symptomatic cerebralemboli as determined by MRI evaluations, frequency, anatomic location,and size (diameter and volume) of cerebral emboli by MRI evaluations atbaseline, post-ablation and during follow-up, incidence of new orworsening neurologic deficits at baseline, post-ablation and follow-upcompared to baseline summary of NIHSS scores at baseline, post-ablationand during follow-up, summary of MoCA scores at baseline, 1 monthfollow-up and during further follow-up, and hospitalization forcardiovascular events (hospitalization defined as prolonged stay nightspost index procedure or in-patient stay not concurrent with indexprocedure 1 calendar day.

Secondary endpoints of the study as to effectiveness included percentage(%) of PVI touch-up by focal catheter among all targeted veins and bysubject; percentage (%) of subjects with use of focal catheter ablationfor non-PV triggers; percentage (%) of subjects with freedom fromdocumented, symptomatic atrial fibrillation (AF), atrial tachycardia(AT), or atypical (left side) atrial flutter (AFL) episodes(episodes >30 seconds on arrhythmia monitoring device from day 91 to180); and percentage (%) of subjects with freedom from documented,atrial fibrillation (AF), atrial tachycardia (AT), or atypical (leftside) atrial flutter (AFL) episodes (episodes >30 seconds on arrhythmiamonitoring device from day 91 to 180).

Secondary endpoints of the study as to additional analyses on proceduralcharacteristics, including but not limited to total procedure time,ablation time, RF application time, balloon dwell time, time to effectPVI, number and time of RF applications per PV location, and fluoroscopytime and dose.

Secondary endpoints of the study as to health economic assessmentsincluded index procedural workflow costs, hospital costs, and quality oflife.

Subjects enrolled in a NAE (Neurological Assessment Evaluable) subgroupare assessed for incidences of symptomatic and asymptomatic pre-ablationand post-ablation cerebral emboli, with either an absence ofneurological symptoms (asymptomatic) or with emboli-associatedneurological symptoms (symptomatic). The NAE subgroup is a prospectivedesign with consecutive enrollment. Roll-in subjects can NOT be eligiblefor the NAE subgroup. This approach minimizes the confounding influenceof a learning curve during early use of a medical device. Enrollment inthe NAE subgroup can be terminated prior to achieving the target 40subjects if study enrollment ends early after a planned interim look.

Subjects enrolled in the Modified Intent-To-Treat (mITT) populationincluded enrolled subjects meeting eligibility criteria and had thestudy catheter inserted. The safety population (SP) included allenrolled subjects who have undergone insertion of the study catheter.The Per Protocol (PP) Population was a subset of the mITT population andincluded subjects enrolled and meet all eligibility criteria, hadundergone RF ablation with the study catheter, and had been treated forthe study-related arrhythmia.

Primary effectiveness endpoints as to clinical effectiveness in thestudy was determined by those events where there was freedom fromdocumented AF, atrial tachycardia (AT), or Atypical (left-side) atrialflutter (AFL) episodes (e.g., >30 seconds on arrhythmia monitoringdevice) based on electrocardiographic data through the effectivenessevaluation period (day 91-365 post index procedure). Additionally, if asubject met any one of the following criteria, then the subject wasconsidered as chronic effectiveness failure: Acute procedural failure(i.e., failure to confirm entrance block in clinically relevantpulmonary veins post-procedure), repeat ablation or surgical treatmentfor AF/AT/Atypical (left-side) AFL after the blanking period (after day90 post index procedure), DC cardioversion for AF/AT/Atypical(left-side) AFL after the blanking period (after day 90 post indexprocedure), continuous AF/AT/AFL on a standard 12-lead ECG even if therecording is less than 30 seconds in duration (after day 90 post indexprocedure), a new Class I and/or Class III AAD is prescribed for AFduring effectiveness evaluation period (e.g., day 91-365 post indexprocedure) or prescribed during the blanking period and continued past90 days, a previously failed Class I and/or Class III AAD (failed at orbefore screening) was taken for AF at a greater dose than the highestineffective historical dose during the effectiveness evaluation period(e.g., day 91-365 post index procedure), and amiodarone was prescribedpost index ablation procedure.

During this study, current AF management guidelines and theinstitution's standard of care practices are followed as closely aspossible for AAD therapy. FIG. 16 shows a table illustratingclassifications based on AAD therapy administered in the blanking andpost-blanking periods in the study.

It is understood that prior to the procedure, uninterruptedanticoagulation therapy was in place at least 1 month prior to theablation procedure. If receiving warfarin/coumadin therapy, subjects hadan international normalized ratio (INR)≥2 for at least 3 weeks prior totreatment and the subject's must be confirmed to be ≥2 within 48 hourspre-procedure. Any INR <2 within 3 weeks prior to ablation wasunderstood to lead to exclusion of the subject or postponement of thestudy procedure until the INR is ≥2 for at least 3 weeks prior totreatment. Anticoagulation therapy was not interrupted or stopped priorto the procedure (e.g., no doses should be missed or omitted) and dailyregimen was continued.

During the procedure, a heparin bolus was administered prior totransseptal puncture an ACT of 350-400 was targeted seconds prior toinserting the balloon 80 and throughout the procedure. ACT levels werechecked every 15-30 minutes during the procedure to ensure an ACT targetof 350-400 seconds. All recordings (ACT level, timing of heparinadministration and dose) were documented in the medical records assource documentation. All tubing and sheath were continuously flushedwith heparinized saline.

After the procedure, anticoagulation therapy was strongly recommendedfor at least 2 months following ablation. Additional medications neededto treat clinical indications were at the discretion of the clinicalinvestigation physician AAD management during the study was at thediscretion of the investigator.

Secondary effectiveness endpoints included acute procedural successdefined as confirmation of entrance block in treated PVs after adenosinechallenge (with or without the use of a focal catheter), PVI touch-up byfocal catheter among all targeted veins and by subject during the indexprocedure, use of focal catheter ablation for non-PV triggers during theindex procedure, freedom from documented symptomatic AF/AT/Atypical(left-side) AFL episodes based on electrocardiographic data through theeffectiveness evaluation period (day 91-365 post index procedure) offType I and III antiarrhythmic drugs (AADs), and average number of RFapplications, and RF time, required to isolate common pulmonary veins.

Patient Selection

The criteria for patient selection, method or uses, personnel,facilities, and training specified in this study were intended tominimize the risk to subjects undergoing this procedure.

Patients were prescreened carefully prior to enrollment in the study toensure compliance with the inclusion and exclusion criteria. The risk ofphrenic nerve paralysis (PNP) was minimized by monitoring the PN withpacing maneuvers before the ablation. Ablation was stopped immediatelyif evidence of PN impairment is observed, and the balloon can berepositioned. The risk of PV stenosis can be minimized by notpositioning the balloon within the tubular portion of the target PV. Theballoon should not be inflated while the catheter is positioned insidethe pulmonary vein; rather, it is always to be inflated in the atrium,then positioned at the PV ostium.

The risk of asymptomatic cerebral emboli (ACE) can be minimized byimplementing an anti-coagulation regimen prior to balloon introductioninto the left atrium and during procedure to avoid thrombi/emboli duringprocedure. Investigators are instructed to remove air bubbles and tominimize catheter exchange during procedure to mitigate the risk of airintroduction. A single transseptal technique, with administration ofheparin bolus prior to transseptal puncture, is also implemented. Inorder to help prevent esophageal injury, intraluminal esophagealtemperature monitoring is required for the study.

Following procedures, all subjects are maintained on systemic oralanticoagulation therapy for at least two months post-procedure,beginning within 6 hours post-procedure. After two-monthspost-procedure, a decision regarding continuation of systemicanti-coagulation agents is made based on the subject's risk forthromboembolism. Systemic oral anticoagulation can be continued beyondtwo-months post-ablation in subjects with Congestive heart failureHypertension Age 75 years or older Diabetes mellitus Stroke, TIA, or TEVascular disease Age 65 to 74 years Sex category (female) (hereafter“CHA₂DS₂-VASc”) score≥2.

For each included patient, age, gender and cardiovascular risk factors(e.g., diabetes mellitus, obesity, smoking, high blood pressure,hyperlipidemia) were recorded. Initial imaging was brain CT withcervical and intracranial angiography or brain MRI with time of flightangiography, depending on hospital protocol. The ASPECT (Alberta StrokeProgram Early CT) score was evaluated by experienced neuroradiologistson either modality, and the NIHSS score by neurologists. Patients weretreated up to 12 hours from time of stroke onset or time last known wellin case of wake-up stroke.

Inclusion criteria for the study included the following:

Diagnosed with Symptomatic PAF, including at least three (3) symptomaticepisodes of AF with attacks lasting ≥1 minute) within six (6) monthsprior to enrollment, and at least one (1) AF episode must beelectrocardiographically documented within twelve (12) months prior toenrollment. Electrocardiographic documentation can include, but is notlimited to, electrocardiogram (ECG), Holter monitor, or telemetry strip;

Selected for AF ablation procedure for pulmonary vein isolation; Ableand willing to comply with uninterrupted per-protocol;

Failing at least one (1) Class I or Class III AAD as evidenced byrecurrent symptomatic AF or intolerable side effects to the AAD;

Willingness to comply with anticoagulation requirements (e.g., warfarin,rivaroxaban, dabigatran, apixaban);

Age 18-75 years; and

Able and willing to comply with all pre-procedure, post-procedure, andfollow-up testing and visit requirements.

Exclusion criteria for the study included the following:

-   -   AF secondary to electrolyte imbalance, thyroid disease, or        reversible or non-cardiac cause;    -   Previous surgical or catheter ablation for AF;    -   Anticipated to receive ablation outside the PV ostia and CTI        region (e.g. AVRT, AVNRT, atrial tachycardia, VT and WPW);    -   Previously diagnosed with persistent or long-standing persistent        AF and/or Continuous AF >7 days, or >48 hrs terminated by        cardioversion;    -   Any percutaneous coronary intervention within the past 2 months;    -   Valve repair or replacement or presence of a prosthetic valve;    -   Any carotid stenting or endarterectomy;    -   Any carotid stenting or endarterectomy.    -   Coronary artery bypass grafting (CABG), cardiac surgery (e.g.        ventriculotomy, atriotomy), or valvular cardiac surgical or        percutaneous procedure within the past 6 months.    -   Documented left atrium (LA) thrombus on baseline/pre-procedure        imaging.    -   LA antero posterior diameter >50 mm    -   Any PV with a diameter 26 mm    -   Left Ventricular Ejection Fraction (LVEF) <40%.    -   Contraindication to anticoagulation (e.g. heparin).    -   History of blood clotting or bleeding abnormalities.    -   Myocardial infarction within the past 2 months.    -   Documented thromboembolic event (including transient ischemic        attack [TIA]) within the past 12 months.    -   Rheumatic Heart Disease.    -   Uncontrolled heart failure or New York Heart Association (NYHA)        function class III or IV.    -   Awaiting cardiac transplantation or other cardiac surgery within        the next 12 months.    -   Unstable angina.    -   Acute illness or active systemic infection or sepsis.    -   Diagnosed atrial myxoma or interatrial baffle or patch.    -   Presence of implanted pacemaker or, implantable cardioverter        defibrillator (ICD), or tissue-embedded, iron-containing metal        fragments.    -   Significant pulmonary disease, (e.g. restrictive pulmonary        disease, constrictive or chronic obstructive pulmonary disease)        or any other disease or malfunction of the lungs or respiratory        system that produces chronic symptoms.    -   Significant congenital anomaly or medical problem that, in the        opinion of the investigator, would preclude enrollment in this        study.    -   Women who are pregnant (as evidenced by pregnancy test if        pre-menopausal), lactating, or who are of child bearing age and        plan on becoming pregnant during the course of the clinical        investigation.    -   Enrollment in an investigational study evaluating another        device, biologic, or drug.    -   Has known pulmonary vein stenosis.    -   Presence of intramural thrombus, tumor or other abnormality that        precludes vascular access, or manipulation of the catheter.    -   Presence of an IVC filter    -   Presence of a condition that precludes vascular access.    -   Life expectancy or other disease processes likely to limit        survival to less than 12 months.    -   Presenting contra-indication for the devices (e.g. TTE, CT,        etc.) used in the study, as indicated in the respective        instructions for use.    -   Categorized as a vulnerable population and requires special        treatment with respect to safeguards of well-being    -   Additional exclusion criteria for Neurological Assessment        Evaluable (NAE) subjects include contraindication    -   Patient on amiodarone at any time during the past 3 months prior        to enrollment;    -   Contraindication to use of contrast agents for MRI such as        advanced renal disease, etc. (at PI discretion), presence of        iron-containing metal fragments in the body, and    -   Unresolved pre-existing neurological deficit.        Results of the Study

During the study, investigators collected the following data: RFablation parameters per PV, number of RF application(s) per target PV,number of RF application(s) required with a focal catheter (ifapplicable), total RF duration per target PV, total time of RFapplication with the balloon catheter 24 until PV isolation of targetedvein was achieved (TTI ˜time to isolate), total time of RF applicationwith the focal catheter (if applicable), PV acute reconnection, RFablation parameters per application, Targeted vein, Ablation number ofthe generator, Total Duration of RF energy per application, BalloonInflation Index prior to target PV application, pacing electrodes,ablation parameters (impedance, temperature, power, number of activeelectrodes per application, and total duration of RF application. Also,RF duration of posterior/anterior electrode, etc.) can be collectedduring the ablation procedure via the generator log files, ablationparameters, including but not limited to percentage of targeted PVisolated on first shot and percentage of targeted PV with acutereconnections, procedural parameters, including but not limited to:Duration of time in mapping (LA and PVs), Total RF duration (consecutivetime of RF energy delivered by multi-electrode RF balloon catheter andfocal catheter (if applicable)), Total PVI time with balloon catheter(Duration of time from 1^(st) RF application to final RF application),Total PVI time with focal catheter (if applicable), Total procedure time(from first femoral puncture to catheter removal), Total fluoroscopytime and dose, Total Balloon dwell time (from first RF balloon insertionuntil RF balloon removal), ECG data, Total fluid delivered via ablationcatheter, Total fluid delivered via intravenous line (if captured),Fluid output (if captured), Net Fluid input, ACT level and timepoint ofheparin administration, Strategy to evaluate the proximity to thephrenic nerve, Strategy used to minimize risk of esophageal injury, Typeof temperature probe, cut-off temperature and any abnormal increases intemperature observed.

FIG. 17 depicts a method or use 1700 for administering a procedure fortreating atrial fibrillation. The method or use 1700 can include 1710delivering a multi-electrode radiofrequency balloon catheter to one ormore targeted pulmonary veins; 1720 ablating tissue of the pulmonaryvein using the multi-electrode radiofrequency balloon catheter; and 1730achieving a predetermined effectiveness rate of pulmonary veinisolation.

FIG. 18 depicts a method or use 1800 for administering a procedure fortreating atrial fibrillation. The method or use 1800 can include 1810delivering a multi-electrode radiofrequency balloon catheter to apulmonary vein; 1820 ablating tissue of the pulmonary vein using themulti-electrode radiofrequency balloon catheter; and 1830 achieving apredetermined effectiveness rate of pulmonary vein isolation.

FIG. 19 depicts a method or use 1900 for administering a procedure fortreating atrial fibrillation. The method or use 1900 can include 1910delivering a multi-electrode radiofrequency balloon catheter to apulmonary vein; 1920 ablating tissue of the pulmonary vein using themulti-electrode radiofrequency balloon catheter; and 1930 achievingpulmonary vein isolation and at least a 97% safety endpoint within seven(7) days of successful pulmonary vein isolation.

FIG. 20 depicts a method or use 2000 for administering a procedure fortreating atrial fibrillation. The method or use 2000 can include 2010delivering a multi-electrode radiofrequency balloon catheter to apulmonary vein; 2020 ablating tissue of the pulmonary vein using themulti-electrode radiofrequency balloon catheter; and 2030 achievingpulmonary vein isolation and at least a 90% safety endpoint within seven(7) days of successful pulmonary vein isolation

FIG. 21 depicts a method or use 2100 for administering a procedure fortreating atrial fibrillation. The method or use 2100 can include 2110delivering a multi-electrode radiofrequency balloon catheter having aplurality of independently controllable electrodes for radiofrequencyablation and a multi-electrode diagnostic catheter to one or moretargeted pulmonary veins; 2120 ablating tissue of the one or moretargeted pulmonary veins with one or more of the plurality of theelectrodes independently controlled multi-electrode radiofrequencyballoon catheter; 2130 diagnosing the one or more targeted pulmonaryveins using the multi-electrode diagnostic catheter; and 2140 achievingat least one of a predetermined clinical effectiveness and acuteeffectiveness of the method or use based on use of the multi-electroderadiofrequency balloon catheter and the multi-electrode diagnosticcatheter in the isolation of the one or more targeted pulmonary vein.

FIG. 22 depicts a method or use 2200 to treat a plurality of patientsfor paroxysmal atrial fibrillation. The method or use 2200 can include2210 delivering a multi-electrode radiofrequency balloon catheter havinga plurality of independently controllable electrodes for radiofrequencyablation and a multi-electrode diagnostic catheter to one or moretargeted pulmonary veins; 2220 ablating tissue of one or more targetedpulmonary veins with one or more of the plurality of the electrodesindependently controlled multi-electrode radiofrequency ballooncatheter; 2230 diagnosing all targeted pulmonary veins using themulti-electrode diagnostic catheter; and 2240 achieving a predeterminedrate of adverse events based on use of the multi-electroderadiofrequency balloon catheter and the multi-electrode diagnosticcatheter in the isolation of all targeted pulmonary veins, during andapproximately 6 months after the method or use.

FIG. 23 depicts a method or use 2300 to treat a plurality of patientsfor paroxysmal atrial fibrillation. The method or use 2300 can include2310 evaluating a number and size of all targeted pulmonary veins andanatomy of the left atrial; 2320 puncturing the transseptal; 2330selectively positioning a multi-electrode esophageal temperaturemonitoring device in the vasculature with respect to all targetedpulmonary veins; 2340 selectively positioning a multi-electroderadiofrequency balloon catheter in the vasculature with respect to alltargeted pulmonary veins, the multi-electrode radiofrequency ballooncatheter having a plurality of independently controllable electrodes forradiofrequency ablation; 2350 ablating tissue of all targeted pulmonaryveins with one or more of the plurality of the electrodes independentlycontrolled multi-electrode radiofrequency balloon catheter; 2360confirming isolation of all targeted pulmonary veins using themulti-electrode diagnostic catheter; 2370 confirming existence of anentrance block in all targeted pulmonary veins; and 2380 achieving apredetermined clinical effectiveness and/or acute effectiveness of themethod or use, based on the confirmed existence of the entrance block,regarding the isolation of all targeted pulmonary veins following themethod or use.

FIG. 24 shows a table summarizing single shot isolation versusnon-isolation according to the study of this disclosure. In particular,FIG. 24 summarizes single shot isolation versus non-isolation accordingto ablation location, number of electrode ablations, initial impedance,impedance drop, maximum temperature, and temperature rise. With respectto the number of electrode ablations, only first ablation with fullcircle and full duration ablations were included for analysis. With thisin mind, the study investigated certain endpoints of the study aspotential predictors for successful isolation. One endpoint investigatedincluded duration and energy, whereby longer duration and higher energywere evaluated as to inducing to higher rate of single shot PVI as shownand discussed herein.

Another endpoint included time to isolation, but no noticeable impact onsuccess of ablations was observed. Another endpoint included inflationindex but no noticeable impact on success of ablations was observed.Another endpoint included initial impedance, whereby higher initialimpedance variation among the full-circle electrodes was evaluated as toleading to lower rate of single-shot PVI (e.g., <30Ω), as shown anddiscussed herein. Another endpoint included impedance drop, whereby adifference of the impedance drop between anterior and posterior wall wasevaluated as to being a possible indicator for the success of ablation,as shown and discussed herein. Another endpoint included maxtemperature, but no noticeable impact on success of ablations wasobserved.

FIG. 25 shows a graph summarizing initial impedance according to thestudy of this disclosure. In particular, FIG. 25 shows mean differenceof initial impedance between anterior and posterior wall as to singleshot isolation (no reconnection), isolation (reconnection), andnon-isolation for patients evaluated in the study of this disclosure.

FIG. 26 shows a graph summarizing temperature rise according to thestudy of this disclosure. In particular, FIG. 26 shows mean differenceof temperature rise between anterior and posterior wall as to singleshot isolation (no reconnection), isolation (reconnection), andnon-isolation for patients evaluated in the study of this disclosure.

FIG. 27 shows a graph summarizing impedance drop according to the studyof this disclosure. In particular, FIG. 27 shows mean difference ofimpedance drop between anterior and posterior wall as to single shotisolation (no reconnection), isolation (reconnection), and non-isolationfor patients evaluated in the study of this disclosure. In the study,the difference of the impedance drop between anterior and posterior wallwas determined to be a possible indicator for the success of ablation.

FIG. 28 shows a graph summarizing maximum temperature according to thestudy of this disclosure. In particular, FIG. 28 shows mean differenceof maximum temperature between anterior and posterior wall as to singleshot isolation (no reconnection), isolation (reconnection), andnon-isolation for patients evaluated in the study of this disclosure.

FIG. 29A shows a graph summarizing initial impedance variation among1-circle electrodes in the study of this disclosure. In particular, FIG.29A summarizes mean initial impedance variation among 1-circleelectrodes for single shot isolation (no reconnection), isolation(reconnection), and non-isolation for patients evaluated in the study ofthis disclosure. It is noted that only first ablation with full circleand full duration ablations were included for analysis. FIG. 29B shows atable summarizing initial impedance variation among 1-circle electrodesin the study of this disclosure.

FIG. 30 shows a graph summarizing single-shot PVI rate in the study ofthis disclosure according to the initial impedance variation among1-circle electrodes. For 27 patients evaluated less than approximatelyabout 20Ω, single-shot PVI was observed at about 85.2%. For 77 patientsevaluated and approximately between 20 to 30Ω, single-shot PVI wasobserved at about 77.9%. For 61 patients evaluated and approximatelybetween 30 to 40Ω, single-shot PVI was observed at about 75.4%. For 34patients evaluated and approximately between about 40 to 50Ω,single-shot PVI was observed at about 67.6%. For 11 patients evaluatedand approximately between about 50 to 60Ω, single-shot PVI was observedat about 36.4%. For 9 patients evaluated and approximately greater thanabout 60Ω, single-shot PVI was observed at about 33.3%.

FIG. 31 shows a graph summarizing time to isolation in the study of thisdisclosure including single shot isolation (no reconnection) atapproximately about 8.1 seconds and isolation (reconnection) atapproximately about 10.9 for patients evaluated in the study of thisdisclosure.

FIG. 32 shows a graph summarizing inflation index in the study of thisdisclosure as to single shot isolation (no reconnection), isolation(reconnection), and non-isolation for patients evaluated in the study ofthis disclosure.

FIG. 33 shows a table summarizing pre- and post-ablation parameters inthe study of this disclosure as to impedance, impedance variation,lowest initial impedance, mean initial impedance, initial impedancevariation, lowest maximum temperature, lowest impedance drop, meanimpedance drop, and impedance drop variation. Excluding roll-in cases,only first shot for each PV with full-circle (e.g., all electrodeburning) and full duration (e.g., 60 sec) were evaluated for analysis,including a total of 219 ablations with 158 single shot isolation.Minitabe Pearson correlations and binary logistic regression models wereused to evaluate each parameter as a potential predictor of single shotisolation (including LCPV and RMPV). It was understood that largercoefficient and lower P-value of the table in FIG. 33, the betterpredictor. In this analysis, the pre-ablation parameters of mean initialimpedance and initial impedance variation were deemed as predictors ofsingle shot isolation. As for post-ablation parameters, lowest impedancedrop and impedance drop variation were similarly deemed as predictors ofsingle shot isolation.

FIG. 34 shows a table summarizing pre-ablation parameters in the studyof this disclosure as to initial temperature, initial impedance, andinitial anterior wall impedance. Predictors of single shot isolationwere those observed with correlation P-value <0.01, including maximuminitial temperature, initial temperature variation, mean initialimpedance, maximum initial impedance, initial impedance variation, meaninitial anterior wall impedance, lowest anterior wall impedance, maximumanterior wall impedance, and anterior wall impedance variation. It isunderstood that anterior wall impedance values were among the anteriorwall electrodes. Minitabe Pearson correlations and binary logisticregression models were used to evaluate each parameter as a potentialpredictor of single shot isolation (including LCPV and RMPV).

FIG. 35 shows a table summarizing post-ablation parameters in the studyof this disclosure as to temperature slope, temperature rise, maximumtemperature, impedance drop, and impedance drop percentage (e.g.,impedance drop/initial impedance). Predictors of single shot isolationwere those observed with correlation P-value <0.01, including meantemperature slope, lowest temperature slope, mean temperature rise,lowest temperature rise, lowest impedance drop, impedance dropvariation, lowest impedance drop percentage, and variation of impedancedrop percentage. Minitabe Pearson correlations and binary logisticregression models were used to evaluate each parameter as a potentialpredictor of single shot isolation (including LCPV and RMPV). As can beseen, in FIGS. 34-35 the mean and highest value of initial impedance andanterior wall initial impedance had high correlation with single shotisolation rate (P value <0.0005). The optimal range (>90% single shotisolate rate) was <95Ω for mean initial impedance and <110Ω for highestinitial impedance.

Based on the data from the SHINE study (with a copy in Appendix 4), itis believed that there are six (6) single-parameter predictor ofsingle-shot-isolation (“SSI”) and eight (8) single-parameter evaluatorfor SSI. The “predictor” allows for a determination of whether therelevant parameters observed or measured (with the study device asdescribed herein) before ablation (i.e., pre-ablation parameters) wouldlikely lead to a success rate of 90% or higher based on the data gleanedfrom the study. The “evaluator” on the other hand, allows for adetermination of whether the actual ablation performed would likely leadto a success rate of 90% or greater for SSI. The “predictor” and“evaluator” are summarized in Table 1 below:

TABLE 1 SINGLE PARAMETER PREDICTORS AND EVALUATORS Potential Predictorsor evaluators (P value < 0.01) Implication Predictor Initial Imp -Variation Initial Impedance variation <20 Ω, single shot isolation (SSI)rate of nearly 90%. Lower variation, higher SSI rate. (Pre- InitialImp - Highest When the highest initial impedance <<110 Ω, SSI rate >90%ablation Initial Imp - Mean When the mean initial impedance <95 Ω, SSIrate >90% parameters) Initial Temp - Highest Highest Initial temp <31°C., SSI rate >90% Initial Temp - Initial temp variation <3° C., SSIrate >90% Variation # of electrodes with # of electrode with initialimpedance deviation from mean value is zero, initial impedance thesingle shot isolation rate is 92.3% (n~13). deviation from mean value≥10 Ω Evaluator Imp drop - Variation Impedance drop Variation <20 Ω, SSIrate >85% (Post- Temp Rise - Lowest Lowest Temp rise ≥6° C., SSIrate >90% Ablation Imp drop - Lowest Lowest Impedance drop ≥12 Ω, SSIrate >90% Parameters) Imp drop percent- Lowest Impedance drop Percent≥12%, single shot isolation rate >90% Lowest Temp Slope - Lowest LowestTemp slope ≥0.75° C./sec, SSI rate >90% Temp Slope - Mean Higher meantemp slope, higher SSI isolation rate Imp drop percent- larger Imp droppercent variation, higher SSI isolation rate variation Temp Rise - MeanMean Temp rise ≥14° C., SSI rate >90%

FIG. 36 shows a table summarizing what is believed to be potentialrankings of pre- and post-ablation parameters from Table 1 above thatwere single shot predictors observed in the study of this disclosure.Regarding pre-ablation parameters, rankings of single shot predictorsfrom first to fifth were initial impedance variation, highest initialtemperature, variation of initial temperature, anterior impedancevariation, and anterior lowest impedance, respectively. Regardingpost-ablation parameters, rankings of single shot predictors from firstto sixth were initial impedance drop variation, lowest temperature rise,lowest impedance drop, lowest temperature slope, mean temperature slope,and mean temperature rise, respectively. Stated differently, the mostaccurate predictor of single shot isolation rate before ablation was (a)achieving small variation in the impedance (e.g., <20Ω) and temperature(<3° C.) among 10 electrodes, (b) limiting the highest initial temp(e.g., <31° C.) of 10 electrodes, and (c) permitting the lowest anteriorwall impedance to range between approximately about 80-90Ω.

FIG. 37 shows a graph summarizing correlations between mean initialimpedance and age of patients in the study of this disclosure. FIG. 38shows a graph summarizing correlations between mean initial impedanceand BMI of patients in the study of this disclosure. FIG. 39 shows agraph summarizing correlations between initial temperature andtemperature rise in the study of this disclosure. FIG. 40 shows a graphsummarizing correlations between initial temperature and temperatureslope in the study of this disclosure. FIG. 41 shows a graph summarizingcorrelations between initial temperature and initial impedance in thestudy of this disclosure. FIG. 42 shows a graph summarizing correlationsbetween initial temperature and impedance drop in the study of thisdisclosure. FIG. 43 shows a graph summarizing correlations betweeninitial temperature variation and highest initial temperature in thestudy of this disclosure. FIG. 44 shows a graph summarizing correlationsbetween initial temperature variation and impedance drop variation inthe study of this disclosure. FIG. 45 shows a graph summarizingcorrelations between initial temperature variation and temperature risevariation in the study of this disclosure.

FIG. 46 shows a graph summarizing correlations between initialtemperature variation and temperature slope variation in the study ofthis disclosure. FIG. 47 shows a graph summarizing correlations betweeninitial impedance and temperature rise in the study of this disclosure.FIG. 48 shows a graph summarizing correlations between initial impedanceand temperature slope in the study of this disclosure. FIG. 49 shows agraph summarizing correlations between initial impedance and impedancedrop in the study of this disclosure. FIG. 50 shows a graph summarizingcorrelations between initial impedance and impedance drop percent in thestudy of this disclosure. FIG. 51 shows a graph summarizing correlationsbetween initial impedance variation and initial temperature variation inthe study of this disclosure. FIG. 52 shows a graph summarizingcorrelations between initial impedance variation and impedance dropvariation in the study of this disclosure. FIG. 53 shows a graphsummarizing correlations between initial impedance variation and highestinitial impedance in the study of this disclosure. FIG. 54 shows a graphsummarizing correlations between initial impedance variation and meaninitial impedance in the study of this disclosure.

FIG. 55 shows a graph summarizing correlations between initial impedancevariation and lowest impedance drop in the study of this disclosure.FIG. 56 shows a graph summarizing correlations between lowesttemperature rise and lowest impedance drop in the study of thisdisclosure. FIG. 57 shows a graph summarizing correlations betweenlowest impedance drop and lowest temperature slope in the study of thisdisclosure. FIG. 58 shows a graph summarizing correlations betweenlowest temperature rise and lowest temperature slope in the study ofthis disclosure.

FIG. 59 shows a schematic summarizing correlative data sets forsingle-shot isolation predictors according to the study of thisdisclosure. In particularly, FIG. 59 demonstrates that pre-ablationparameter data sets such as temperature rise, initial temperature, andtemperature slope were deemed to have strong correlations to single-shotisolation predictors for single-shot isolation. Similarly, FIG. 59demonstrates that pre-ablation parameter data sets such as impedancedrop variation, initial impedance variation, and highest initialimpedance were deemed to have very strong correlations to single-shotisolation predictors for single-shot isolation. It is contemplated thatthe solution of this disclosure may use multiple parameters (as opposedto a single-parameter for predictor and evaluator referenced in theTable) such as, for example, initial temperature variation, highestinitial temperature, initial impedance variation, and highest initialimpedance as pre-ablation predictors of single-shot isolation. Table 2summarizes the parameters utilized for the multi-parameter predictorsand evaluators.

TABLE 2 MULTIPLE-PARAMETERS PREDICTORS AND EVALUATORS Combination ofmultiple parameters Temperature parameter Impedance parameter PredictorPredictor-1 Initial temperature variation Initial impedance variationPredictor-2 Highest initial impedance Predictor-3 Mean initial impedancePredictor-4 Highest initial temperature Initial impedance variationPredictor-5 Highest initial impedance Predictor-6 Mean initial impedancePredictor-7 Initial temperature variation & initial impedance variation& Highest Highest initial temperature initial impedance EvaluatorEvaluator-1 Lowest Temperature rise Impedance drop variation Evaluator-2Lowest impedance drop Evaluator-3 Lowest impedance drop & impedance dropvariation Evaluator-4 impedance drop percent variation Evaluator-5Lowest impedance drop percent Evaluator-6 Lowest impedance drop percent& impedance drop percent variation

FIG. 60 shows a schematic summarizing correlative data sets forsingle-shot isolation evaluators according to the study of thisdisclosure. FIG. 60 demonstrates that post-ablation parameter data setssuch as lowest temperature slope, lowest temperature rise, lowestimpedance drop, impedance drop variation, lowest impedance drop, andimpedance drop variation were deemed to have strong correlations tosingle-shot isolation evaluators for single-shot isolation. It iscontemplated that the solution of this disclosure may use one or more ofthese parameters as post-ablation evaluators of single-shot isolation.Taking into account the foregoing, one example algorithm that iscontemplated for use as a predictor of single shot isolation includesthe following:

${Probability} \sim \frac{e^{Y}}{( {1 + e^{Y}} )}$Y∼4.367 − 0.420 Δ T₀ − 0.0486 Δ Z₀

Where single shot isolation probability is a function of two parameters:initial impedance variation (ΔT₀) and initial temperature variation(ΔZ₀).

FIG. 61A shows a computer simulation model executing the aforementionedsingle shot isolation probability algorithm while FIGS. 61B-61C showtables summarizing data associated with the simulation of FIG. 61A.

Another example algorithm contemplated for use as a predictor of singleshot isolation includes the following:

${Prob}\text{∼}\frac{e^{Y}}{( {1 + e^{Y}} )}$Y∼26.78 − 0.576T_(0 max ) − 0.0632 Z_(0max )

Where the predictor algorithm includes two parameters: highest initialtemperature (T_(0max)) and highest initial impedance (Z_(0max)). FIG.62A shows a computer simulation model executing the aforementionedexample algorithm while FIGS. 62B-62C show tables summarizing dataassociated with the simulation of FIG. 62A.

Another example algorithm contemplated for use as a predictor of singleshot isolation includes the following:

${Prob}\text{∼}\frac{e^{Y}}{( {1 + e^{Y}} )}$Y∼27.70 − 0.540 T_(0max ) − 0.0959 Z_(0max )

Where the predictor algorithm includes two parameters: highest initialtemperature (T_(0max)) and highest initial impedance (Z_(0max)). FIG.63A shows a computer simulation model executing the aforementionedexample algorithm while FIGS. 63B-63C show tables summarizing dataassociated with the simulation of FIG. 63A.

Another example algorithm contemplated for use as a predictor of singleshot isolation includes the following:

${Prob}\text{∼}\frac{e^{Y}}{( {1 + e^{Y}} )}$Y∼9.31 − 0.408 Δ T₀ − 0.0544 Z_(0max )

Where the predictor algorithm includes two parameters: initialtemperature variation (ΔT₀) and highest initial impedance (Z_(0max)).FIG. 64A shows a computer simulation model executing the aforementionedexample algorithm while FIGS. 64B-64C show tables summarizing dataassociated with the simulation of FIG. 64A.

Another example algorithm contemplated for use as a predictor of singleshot isolation includes the following:

${Prob}\text{∼}\frac{e^{Y}}{( {1 + e^{Y}} )}$Y∼11.53 − 0.439 Δ T₀ − 0.0856  Z_(0mean)

Where the predictor algorithm includes two parameters: initialtemperature variation (ΔT₀) and mean initial impedance (Z_(0mean)). FIG.65A shows a computer simulation model executing the aforementionedexample algorithm while FIGS. 65B-65C show tables summarizing dataassociated with the simulation of FIG. 65A.

Another example algorithm contemplated for use as a predictor of singleshot isolation includes the following:

${Prob}\text{∼}\frac{e^{Y}}{( {1 + e^{Y}} )}$Y∼22.61 − 0.622 T_(0max ) − 0.0626 Δ Z₀

Where the predictor algorithm includes two parameters: highest initialtemperature (T_(0max)) and initial impedance variation (ΔZ₀). FIG. 66Ashows a computer simulation model executing the aforementioned examplealgorithm while FIGS. 66B-66C show tables summarizing data associatedwith the simulation of FIG. 66A.

Another example algorithm contemplated for use as a predictor of singleshot isolation includes the following:

${Prob}\text{∼}\frac{e^{Y}}{( {1 + e^{Y}} )}$Y∼26.52 + 0.013 Δ T₀ − 0.594 T_(0max ) − 0.0122 Δ Z₀ − 0.0535 Z_(0max )

Where the predictor algorithm includes four parameters: initialtemperature variation (ΔT₀), highest initial temperature (T_(0max)),initial impedance variation (ΔZ₀) and highest initial impedance(Z_(0max)). FIG. 67 shows a table summarizing data associated with asimulation of this example algorithm.

Another example algorithm contemplated for use as an evaluator of singleshot isolation includes the following:

${Prob}\text{∼}\frac{e^{Y}}{( {1 + e^{Y}} )}$Y∼1.562 + 0.2856 Δ T_(min) − 0.0629 Δ Z_(drop)

Where the evaluator algorithm includes two parameters: lowesttemperature rise (ΔT_(min)) and impedance drop variation (ΔZ_(drop)).FIG. 68A shows a computer simulation model executing the aforementionedexample algorithm while FIGS. 68B-68C show tables summarizing dataassociated with the simulation of FIG. 68A.

Another example algorithm contemplated for use as an evaluator of singleshot isolation includes the following:

$P\text{∼}\frac{e^{Y}}{( {1 + e^{Y}} )}$Y∼ − 0.507 + 0.206Δ T_(min) + 0.083  Z_(dropmin)

Where the evaluator algorithm includes two parameters: lowesttemperature rise (ΔT_(min)) and minimum impedance drop (Z_(dropmin)).FIG. 69A shows a computer simulation model executing the aforementionedexample algorithm while FIGS. 69B-69C show tables summarizing dataassociated with the simulation of FIG. 69A.

Another example algorithm contemplated for use as an evaluator of singleshot isolation includes the following:

$P\text{∼}\frac{e^{Y}}{( {1 + e^{Y}} )}$Y∼1.248 + 0.2486 Δ T_(min) − 0.0594 Δ Z_(drop) + 0.0419  Z_(dropmin)

Where the evaluator algorithm includes three parameters: lowesttemperature rise (ΔT_(min)), impedance drop variation (ΔZ_(drop)) andlowest impedance drop (Z_(dropmin)). FIG. 70A-FIG. 70B show tablessummarizing data associated with a simulation of above-referencedexample algorithm.

Another example algorithm contemplated for use as an evaluator of singleshot isolation includes the following:

$P\text{∼}\frac{e^{Y}}{( {1 + e^{Y}} )}$Y∼1.174 + 0.2515 Δ T_(min) − 0.0564 Δ Z_(drop)  %

Where the evaluator algorithm includes two parameters: lowesttemperature rise (ΔT_(min)), and impedance drop percent variation (ΔZ_(drop)%). FIG. 71A shows a computer simulation model executing theaforementioned example algorithm while FIGS. 71B-71C show tablessummarizing data associated with the simulation of FIG. 71A.

Another example algorithm contemplated for use as an evaluator of singleshot isolation includes the following:

$P\text{∼}\frac{e^{Y}}{( {1 + e^{Y}} )}$Y∼ − 0.644 + 0.170 Δ T_(min) + 0.107 Z_(drop)  %_(min)

Where the evaluator algorithm includes two parameters: lowesttemperature rise (ΔT_(min)), and lowest impedance drop percent(Z_(drop)%_(min)). FIG. 72A shows a computer simulation model executingthe aforementioned example algorithm while FIGS. 72B-72C show tablessummarizing data associated with the simulation of FIG. 72A.

Another example algorithm contemplated for use as an evaluator of singleshot isolation includes the following:

$P\text{∼}\frac{e^{Y}}{( {1 + e^{Y}} )}$Y∼0.339 + 0.187 Δ T_(min) + 0.0737  Z_(drop)  %_(min) − 0.0368 Δ Z_(drop)  %

Where the evaluator algorithm includes three parameters: lowesttemperature rise (ΔT_(min)), lowest impedance drop Percent(Z_(drop)%_(min)) and impedance drop percent variation (Δ Z_(drop)%).FIG. 73A-FIG. 73B show tables summarizing data associated with asimulation of above-referenced example algorithm.

Another example algorithm contemplated for use as an evaluator of singleshot isolation includes the following:

$P\text{∼}\frac{e^{Y}}{( {1 + e^{Y}} )}$Y∼1.043 + 0.777 T_(min)^(′) + 0.171 Δ T_(min) + 0.0479  Z_(drop − min ) − 0.0589 Δ Z_(drop)

Where the evaluator algorithm includes four parameters: lowesttemperature slope (T′_(min)), lowest temperature rise (ΔT_(min)), lowestimpedance drop (Z_(drop-min)) and impedance drop variation (ΔZ_(drop)).FIG. 74 shows a table summarizing data associated with the simulation ofthe referenced evaluator algorithm.

FIG. 75A shows a bar graph summarizing single shot isolation probabilityversus pre-ablation mean initial temperature while FIG. 75B shows abinary fitted line plot of single shot isolation probability versuspre-ablation mean initial temperature in the study of this disclosure.As can be seen, at a mean initial temperature of approximately less thanabout 28° C., the single shot isolation rate was approximately about90%. The P-value of FIG. 75B was 0.016 with an odds ratio (95% CI) of0.714 (0.536-0.951).

FIG. 76A shows a bar graph summarizing single shot isolation probabilityversus pre-ablation lowest initial temperature while FIG. 76B shows abinary fitted line plot of single shot isolation probability versuspre-ablation lowest initial temperature in the study of this disclosure.The single shot isolation rate was approximately about 90%. The P-valueof FIG. 76B was 0.191 with an odds ratio (95% CI) of 0.815(0.580-1.111).

FIG. 77A shows a bar graph summarizing single shot isolation probabilityversus pre-ablation highest initial temperature while FIG. 77B shows abinary fitted line plot of single shot isolation probability versuspre-ablation highest initial temperature in the study of thisdisclosure. The single shot isolation rate was approximately about 90%when the highest initial temperature was less than approximately 31° C.The P-value of FIG. 77B was 0.000 with an odds ratio (95% CI) of 0.609(0.448-0.828).

FIG. 78A shows a bar graph summarizing single shot isolation probabilityversus pre-ablation initial temperature variation while FIG. 78B shows abinary fitted line plot of single shot isolation probability versuspre-ablation initial temperature variation in the study of thisdisclosure. The single shot isolation rate was greater thanapproximately about 95% when the initial temperature variation was lessthan approximately 3° C. The P-value of FIG. 78B was 0.002 with an oddsratio (95% CI) of 0.624 (0.460-0.847).

FIG. 79A shows a bar graph summarizing single shot isolation probabilityversus pre-ablation distributed initial temperature while FIG. 79B showsa binary fitted line plot of single shot isolation probability versuspre-ablation distributed initial temperature in the study of thisdisclosure. As can be seen, at a distributed initial temperature ofapproximately greater than about 31° C., the single shot isolation ratewas greater than approximately about 90%. The P-value of FIG. 59B was0.040 with an odds ratio (95% CI) of 0.832 (0.699-0.991).

FIG. 80A shows a bar graph summarizing single shot isolation probabilityversus pre-ablation distributed initial temperature while FIG. 79B showsa binary fitted line plot of single shot isolation probability versuspre-ablation distributed initial temperature in the study of thisdisclosure. As can be seen, at a distributed initial temperature ofapproximately greater than about 30° C., the single shot isolation ratewas greater than approximately about 90%. The P-value of FIG. 60B was0.068 with an odds ratio (95% CI) of 0.886 (0.777-1.010).

FIG. 81A shows a bar graph summarizing single shot isolation probabilityversus pre-ablation distributed initial temperature while FIG. 81B showsa binary fitted line plot of single shot isolation probability versuspre-ablation distributed initial temperature in the study of thisdisclosure. As can be seen, at a distributed initial temperature ofapproximately greater than about 29° C., the single shot isolation ratewas approximately about 90%. The P-value of FIG. 81B was 0.019 with anodds ratio (95% CI) of 0.872 (0.776-0.980).

FIG. 82A shows a bar graph summarizing single shot isolation probabilityversus pre-ablation mean initial impedance while FIG. 82B shows a binaryfitted line plot of single shot isolation probability versuspre-ablation mean initial impedance in the study of this disclosure. Ascan be seen, at an optimal range of approximately less than about 95Ω,the single shot isolation rate was greater than approximately about91.7%. The P-value of FIG. 82B was 0.000 with an odds ratio (95% CI) of0.916 (0.877-0.956).

FIG. 83A shows a bar graph summarizing single shot isolation probabilityversus pre-ablation lowest initial impedance while FIG. 83B shows abinary fitted line plot of single shot isolation probability versuspre-ablation lowest initial impedance in the study of this disclosure.The P-value of FIG. 83B was 0.026 with an odds ratio (95% CI) of 0.950(0.906-0.995).

FIG. 84A shows a bar graph summarizing single shot isolation probabilityversus pre-ablation highest initial impedance while FIG. 84B shows abinary fitted line plot of single shot isolation probability versuspre-ablation highest initial impedance in the study of this disclosure.As can be seen, at an optimal range of approximately less than about110Ω, the single shot isolation rate was greater than approximatelyabout 91.7%. The P-value of FIG. 84B was 0.000 with an odds ratio (95%CI) of 0.945 (0.922-0.969).

FIG. 85A shows a bar graph summarizing single shot isolation probabilityversus pre-ablation initial impedance variation while FIG. 85B shows abinary fitted line plot of single shot isolation probability versuspre-ablation initial impedance variation in the study of thisdisclosure. As can be seen, at an optimal range of approximately lessthan about 20Ω, the single shot isolation rate was greater thanapproximately about 88.5%. The P-value of FIG. 85B was 0.000 with anodds ratio (95% CI) of 0.950 (0.927-0.975).

FIG. 86A shows a bar graph summarizing single shot isolation probabilityversus pre-ablation initial anterior wall impedance while FIG. 86B showsa binary fitted line plot of single shot isolation probability versuspre-ablation initial anterior wall impedance in the study of thisdisclosure. As can be seen, at an optimal range of approximately lessthan about 95Ω, the single shot isolation rate was nearly approximatelybetween 87 to 89.7%. The P-value of FIG. 86B was 0.000 with an oddsratio (95% CI) of 0.924 (0.885-0.964).

FIG. 87A shows a bar graph summarizing single shot isolation probabilityversus pre-ablation lowest initial anterior wall impedance while FIG.87B shows a binary fitted line plot of single shot isolation probabilityversus pre-ablation lowest initial anterior wall impedance in the studyof this disclosure. As can be seen, at an optimal range of about 80-90Ω,the single shot isolation rate was nearly approximately between 85.7 to87.5%. The P-value of FIG. 87B was 0.005 with an odds ratio (95% CI) of0.940 (0.898-0.983).

FIG. 88A shows a bar graph summarizing single shot isolation probabilityversus pre-ablation highest initial anterior wall impedance while FIG.88B shows a binary fitted line plot of single shot isolation probabilityversus pre-ablation highest initial anterior wall impedance in the studyof this disclosure. As can be seen, at an optimal range of about 110Ω,the single shot isolation rate was nearly approximately between 88.9 to96.9%. The P-value of FIG. 67B was 0.000 with an odds ratio (95% CI) of0.950 (0.926-0.974).

FIG. 89A shows a bar graph summarizing single shot isolation probabilityversus pre-ablation initial anterior wall impedance variation while FIG.89B shows a binary fitted line plot of single shot isolation probabilityversus pre-ablation initial anterior wall impedance variation in thestudy of this disclosure. As can be seen, at a range of less than about20Ω, the single shot isolation rate was nearly approximately between87.5 to 89.5%. The P-value of FIG. 89B was 0.003 with an odds ratio (95%CI) of 0.962 (0.936-0.988).

FIG. 90A shows a bar graph summarizing single shot isolation probabilityversus pre-ablation mean temperature slope while FIG. 90B shows a binaryfitted line plot of single shot isolation probability versuspre-ablation mean temperature slope in the study of this disclosure. TheP-value of FIG. 90B was 0.003 with an odds ratio (95% CI) of 6.145(1.754-21.529).

FIG. 91A shows a bar graph summarizing single shot isolation probabilityversus pre-ablation lowest temperature slope while FIG. 91B shows abinary fitted line plot of single shot isolation probability versuspre-ablation lowest temperature slope in the study of this disclosure.As can be seen, at a range of greater or equal than about 0.75° C./sec,the single shot isolation rate was greater than approximately 90%. TheP-value of FIG. 91B was 0.001 with an odds ratio (95% CI) of 7.251(2.023-25.983).

FIG. 92A shows a bar graph summarizing single shot isolation probabilityversus pre-ablation highest temperature slope while FIG. 92B shows abinary fitted line plot of single shot isolation probability versuspre-ablation highest temperature slope in the study of this disclosure.The P-value of FIG. 92B was 0.129 with an odds ratio (95% CI) of 1.614(0.860-3.029).

FIG. 93A shows a bar graph summarizing single shot isolation probabilityversus pre-ablation temperature slope variation while FIG. 93B shows abinary fitted line plot of single shot isolation probability versuspre-ablation temperature slope variation in the study of thisdisclosure. The P-value of FIG. 93B was 0.837 with an odds ratio (95%CI) of 0.943 (0.541-1.644).

FIG. 94A shows a bar graph summarizing single shot isolation probabilityversus pre-ablation mean temperature rise while FIG. 94B shows a binaryfitted line plot of single shot isolation probability versuspre-ablation mean temperature rise in the study of this disclosure. Ascan be seen, for a mean temperature rise of equal to or greater thanabout 14° C., the single shot isolation rate was greater thanapproximately 90%. The P-value of FIG. 94B was 0.003 with an odds ratio(95% CI) of 1.170 (1.050-1.304).

FIG. 95A shows a bar graph summarizing single shot isolation probabilityversus pre-ablation lowest value temperature rise while FIG. 95B shows abinary fitted line plot of single shot isolation probability versuspre-ablation lowest value temperature rise in the study of thisdisclosure. As can be seen, for a lowest temperature rise of equal to orgreater than about 6° C., the single shot isolation rate was greaterthan approximately 90%. The P-value of FIG. 95B was 0.000 with an oddsratio (95% CI) of 1.320 (1.122-1.553).

FIG. 96A shows a bar graph summarizing single shot isolation probabilityversus pre-ablation highest value temperature rise while FIG. 96B showsa binary fitted line plot of single shot isolation probability versuspre-ablation highest value temperature rise in the study of thisdisclosure. The P-value of FIG. 96B was 0.126 with an odds ratio (95%CI) of 1.053 (0.985-1.125).

FIG. 97A shows a bar graph summarizing single shot isolation probabilityversus pre-ablation temperature rise variation while FIG. 97B shows abinary fitted line plot of single shot isolation probability versuspre-ablation temperature rise variation in the study of this disclosure.The P-value of FIG. 97B was 0.546 with an odds ratio (95% CI) of 0.979(0.914-1.049).

FIG. 98A shows a bar graph summarizing single shot isolation probabilityversus pre-ablation maximum mean temperature while FIG. 98B shows abinary fitted line plot of single shot isolation probability versuspre-ablation maximum mean temperature in the study of this disclosure.The P-value of FIG. 98B was 0.010 with an odds ratio (95% CI) of 1.189(1.039-1.359).

FIG. 99A shows a bar graph summarizing single shot isolation probabilityversus pre-ablation lowest value maximum temperature while FIG. 99Bshows a binary fitted line plot of single shot isolation probabilityversus pre-ablation lowest value maximum temperature in the study ofthis disclosure. The P-value of FIG. 99B was 0.022 with an odds ratio(95% CI) of 1.250 (1.022-1.528).

FIG. 100A shows a bar graph summarizing single shot isolationprobability versus pre-ablation highest value maximum temperature whileFIG. 100B shows a binary fitted line plot of single shot isolationprobability versus pre-ablation highest value maximum temperature in thestudy of this disclosure. The P-value of FIG. 100B was 0.162 with anodds ratio (95% CI) of 1.050 (0.980-1.125).

FIG. 101A shows a bar graph summarizing single shot isolationprobability versus pre-ablation maximum temperature variation while FIG.101B shows a binary fitted line plot of single shot isolationprobability versus pre-ablation maximum temperature variation in thestudy of this disclosure. The P-value of FIG. 101B was 0.576 with anodds ratio (95% CI) of 1.021 (0.950-1.097).

FIG. 102A shows a bar graph summarizing single shot isolationprobability versus pre-ablation mean impedance drop while FIG. 102Bshows a binary fitted line plot of single shot isolation probabilityversus pre-ablation mean impedance drop in the study of this disclosure.The P-value of FIG. 102B was 0.805 with an odds ratio (95% CI) of 1.008(0.944-1.077).

FIG. 103A shows a bar graph summarizing single shot isolationprobability versus pre-ablation lowest value impedance drop while FIG.103B shows a binary fitted line plot of single shot isolationprobability versus pre-ablation lowest value impedance drop in the studyof this disclosure. As can be seen, when the impedance drop is at arange of greater than or equal to approximately about 12Ω, the singleshot isolation rate was greater than approximately 90%. The P-value ofFIG. 103B was 0.000 with an odds ratio (95% CI) of 1.146 (1.057-1.243).

FIG. 104A shows a bar graph summarizing single shot isolationprobability versus pre-ablation highest value impedance drop while FIG.104B shows a binary fitted line plot of single shot isolationprobability versus pre-ablation highest value impedance drop in thestudy of this disclosure. The P-value of FIG. 104B was 0.022 with anodds ratio (95% CI) of 0.964 (0.934-0.995).

FIG. 105A shows a bar graph summarizing single shot isolationprobability versus pre-ablation impedance drop variation while FIG. 105Bshows a binary fitted line plot of single shot isolation probabilityversus pre-ablation impedance drop variation in the study of thisdisclosure. As can be seen, when the impedance drop variation is at arange of less than approximately about 20Ω, the single shot isolationrate was greater than approximately 85%. The P-value of FIG. 105B was0.000 with an odds ratio (95% CI) of 0.941 (0.911-0.972).

FIG. 106A shows a bar graph summarizing single shot isolationprobability versus pre-ablation lowest value impedance drop percentwhile FIG. 106B shows a binary fitted line plot of single shot isolationprobability versus pre-ablation lowest value impedance drop percent inthe study of this disclosure. As can be seen, when the lowest impedancedrop percent is at a range of greater than or equal to approximatelyabout 12%, the single shot isolation rate was greater than approximately90%. The P-value of FIG. 106B was 0.000 with an odds ratio (95% CI) of1.166 (1.077-1.263).

FIG. 107A shows a bar graph summarizing single shot isolationprobability versus pre-ablation impedance drop percent variation whileFIG. 107B shows a binary fitted line plot of single shot isolationprobability versus pre-ablation impedance drop percent variation in thestudy of this disclosure. As can be seen, at an impedance drop variationrange of less than 20Ω, the single shot isolation rate was greater thanapproximately 85%. The P-value of FIG. 107B was 0.004 with an odds ratio(95% CI) of 0.931 (0.887-0.978).

FIG. 108A shows a bar graph summarizing single shot isolationprobability versus pre-ablation initial impedance deviation from meanvalue while FIG. 108B shows a binary fitted line plot of single shotisolation probability versus pre-ablation initial impedance deviationfrom mean value in the study of this disclosure. As can be seen, whenthe number of electrodes with initial impedance deviation from meanvalue is zero, the single shot isolation rate is approximately about92.3% (n˜13). The P-value of FIG. 108B was 0.009 with an odds ratio (95%CI) of 0.821 (0.708-0.953).

FIG. 109 shows a table summarizing predictors associated withcorresponding Pearson correlation and binary logistic regression valuesin the study of this disclosure. In particular, the table shows thatamong ten electrodes that predictors of the study included (a) thenumber of electrodes with initial impedance at least 10Ω higher thanmean value, (b) the number of electrodes with initial impedance at least10Ω lower than mean value, and (c) the number of electrodes with initialimpedance at least 10Ω higher or lower than mean value.

FIG. 110 shows a table summarizing pre- and post-ablation parameters inthe study of this disclosure as to impedance, impedance variation,lowest initial impedance, mean initial impedance, initial impedancevariation, lowest maximum temperature, lowest impedance drop, meanimpedance drop, and impedance drop variation. Excluding roll-in cases inthe SHINE clinical study, there were 95 cases (including 8 roll-in),only first shot for each PV with full-circle (e.g., all electrodeburning) and full duration (e.g., 60 sec) were evaluated for analysis(with Minitab tool), including a total of 211 ablations with 156 singleshot isolation (excluding left-common-pulmonary-vein (“LCPV”) andright-middle-pulmonary-vein (“RMPV”)). Minitabe Pearson correlations andbinary logistic regression models were used to evaluate each parameteras a potential predictor of single shot isolation (including LCPV andRMPV). It was understood that larger coefficient and lower P-value ofthe table in FIG. 110, the better predictor. In this analysis, thepre-ablation parameters of mean initial impedance and initial impedancevariation were deemed as predictors of single shot isolation, similar toFIG. 109. As for post-ablation parameters, lowest impedance drop andimpedance drop variation were similarly deemed as predictors of singleshot isolation, also similar to FIG. 109.

FIG. 111 shows a binary fitted line plot of probability of single shotisolation versus pre-ablation lowest anterior impedance in the study ofthis disclosure. FIG. 112 shows a binary fitted line plot of probabilityof single shot isolation versus pre-ablation anterior impedancevariation in the study of this disclosure. FIG. 113 shows a binaryfitted line plot of probability of single shot isolation versuspre-ablation lowest impedance in the study of this disclosure. FIG. 114shows a binary fitted line plot of probability of single shot isolationversus pre-ablation mean impedance in the study of this disclosure. FIG.115 shows a binary fitted line plot of probability of single shotisolation versus pre-ablation impedance variation in the study of thisdisclosure. FIG. 116 shows a binary fitted line plot of probability ofsingle shot isolation versus post-ablation lowest maximum temperature inthe study of this disclosure. FIG. 117 shows a binary fitted line plotof probability of single shot isolation versus post-ablation lowestimpedance drop in the study of this disclosure. FIG. 118 shows a binaryfitted line plot of probability of single shot isolation versuspost-ablation mean impedance drop in the study of this disclosure. FIG.119 shows a binary fitted line plot of probability of single shotisolation versus post-ablation impedance drop variation in the study ofthis disclosure.

FIG. 120A shows a graph summarizing single shot electrode temperatureversus time for of electrodes of the balloon catheter used in the studyof this disclosure, while FIG. 120B shows a graph summarizing singleshot electrode impedance versus time for electrodes of the ballooncatheter used in the study of this disclosure. FIG. 121 shows a tablesummarizing impedance and temperature values from the graphs of FIGS.120A-120B. In the summarized example data, the balloon catheter wasplaced at the lesion site and initial temperature and impedancemeasurements were taken to determine as a predictor of PVI success rate.

Initial temperature values of FIGS. 120A-120B were observed as havingrelatively low values with a relatively narrow range determined to bedesireable for being an predictor of PVI success rate more so than theabsolute values of temperature readings being within a predeterminedrange. Absolute temperature of electrodes of the balloon catheteranalyzed depended on tissue-touch, blood temperature, and/or irrigationtemperature. Generally, temperature was observed as being lessinfluenced by patient and tissue type, and was not usually subject to RFgeneration artifacts.

In FIGS. 120A-120B, it was further observed that initial impedancevalues having relatively high values with a relatively narrow range wereeffective as a predictor of PVI success rate, more so than the absolutevalues of impedance readings being within a predetermined range.Absolute impedance can depend on patient, tissue type and the degree ofcontact and generally speaking, impedance can be influenced by RFgeneration artifacts (e.g., interference, calibration, leakage). Incertain examples, an extreme impedance drop can be a predictor of poorcontact.

FIG. 122 shows a table demonstrating temperature and impedance trends inelectrodes of the balloon catheter as to single shot versusnon-isolation comparison for cases of the study of this disclosure. Bymonitoring the temperature of the balloon catheter before and duringablation, PVI success can be predicted. The information summarized inthis table was observed as being particularly useful in predicting PVIsuccess by using temperature and impedance in tandem, pre-ablationand/or during ablation, since both parameters can provide feedback in acomplimentary manner.

FIG. 123A shows a graph summarizing electrode temperature versus time inthe study of this disclosure, while FIG. 123B shows a graph summarizingelectrode impedance versus time in the study of this disclosure. FIG.124 shows a graph summarizing electrode impedance phase versus time inthe study of this disclosure.

During the ablation of FIG. 123B to FIG. 124, the temperature andimpedance measurements may be taken to provide an indication of theultimate success of the ablation procedure. An impedance drop wasexpected and the impedance drop of FIG. 123B to FIG. 124 was observed assimilar for each electrode and significant. Observing the data of FIG.123B to FIG. 124, using temperature, impedance, and/or impedance phasechange parameters during ablation was an indicator of PVI success ratewhen using the balloon catheter of this disclosure.

FIG. 125 depicts a method or use 12500 to treat a predetermined patientpopulation for paroxysmal atrial fibrillation. The method or use 12510can include ablating tissue of one or more targeted pulmonary veins withone or more of a plurality of the electrodes of an independentlycontrolled multi-electrode radiofrequency balloon catheter, the ballooncatheter comprising the plurality of electrodes for radiofrequencyablation that are independently controllable; 12520 determining acharacteristic, based on ablation parameters of the balloon catheter, ofsingle shot pulmonary vein isolation (PVI) success rate; 12530achieving, based on the characteristic and step of ablating tissue, asingle shot isolation PVI success rate in the isolation of all targetedpulmonary veins for the predetermined patient population; and 12540displaying the characteristic and the electrodes energized during theablating.

FIG. 126 depicts a method or use 12600 to treat a predetermined patientpopulation for paroxysmal atrial fibrillation. The method or use 12610can include ablating tissue of one or more targeted pulmonary veins withone or more of a plurality of the electrodes of an independentlycontrolled multi-electrode radiofrequency balloon catheter, the ballooncatheter comprising the plurality of electrodes for radiofrequencyablation that are independently controllable; 12620 determining acharacteristic, based on ablation parameters of the balloon catheter, ofsingle shot pulmonary vein isolation (PVI) success rate; and 12630achieving, based on the characteristic and step of ablating tissue, asingle shot isolation PVI success rate in the isolation of all targetedpulmonary veins for the predetermined patient population. The method oruse can include 12640 displaying the characteristic and identity ofelectrodes that were energized during the ablating. Additionally, oroptionally, a graphical representation of the characteristic (e.g.,predictor or evaluator) and the identity of the electrodes energizedduring the ablating in a graphical display such as, for example, thatshown in FIG. 128.

FIG. 127 illustrates an exemplary flow chart of the subroutine todetermine a probability of success P from either the single-parameterpredictor/evaluator (Table 1) or the multi-parameter predictor/evaluator(Table 2). The subroutine starts with step 1270 whereby the processorinitiates a low current signal to be sent from the generator to each ofthe ten electrodes and the body patch (also known as the indifferentelectrode). The processor also collects measurement of temperatures atstep 1272 from the thermocouple or temperature sensor proximate each ofthe electrode. The temperature values are logged into the memory of theprocessor for analysis in step 1274. The processor retrieves themeasured temperature values and derives the (a) initial temperaturevariation ΔT₀; (b) highest initial temperature T_(0max); (c) lowesttemperature rise ΔT_(min). At step 1282, the processor retrieves thedata logged impedance measurements and derive (a) initial impedancevariation ΔZ₀; (b) highest initial impedance Z_(0max); (c) mean initialimpedance Z_(0mean); (d) impedance drop variation ΔZ_(drop); (e) lowestimpedance drop Z_(dropmin); (f) impedance drop percent variation ΔZ_(drop)%; and (g) lowest impedance drop percent Z_(drop)%_(min).

If the ablation is not completed at step 1284, the processor continuesto collect temperature and impedance values in steps 1272-1282. On theother hand, if the first ablation has been completed then a decisionmoves to step 1286 which references a look-up table (e.g., Table 1)which is used to determine in step 1288 a probability of success using asingle parameter (either temperature or impedance). The processor movesto step 1290 to calculate a probability of success using more than asingle parameter based on the data from the SHINE study. The processormay use one or more of the Y term derived in data storage 1290 for theequation in step 1292. At step 1294, an output of either the singleparameter probability of success in Step 1288 or the multi-parameterprobability of success in step 1292. The system may display both thesingle-parameter probability of step 1288 and the multi-parameterprobability of success of step 1292 as a form of cross-checking foraccuracy.

An exemplary graphical-user-interface and display 1300 is reflected inFIG. 128. GUI display 1300 provides summary information or statistics ofthe ablation procedure for an electrode that a physician may find usefulin making determinations of further therapy. As shown, electrode icon1320 is highlighted such that the information provided corresponds to afirst electrode. A visual indicator 1322 of the probability P of successcan be provided before the actual ablation or as well after the ablationon the GUI display 1300. The visual indicator 1322 can be providedbefore, during or after the first ablation for consideration by thephysician as to whether to continue with one or more subsequentablations. Subsequent ablations are sometimes needed to ensure that allthe tissues giving rise to erratic signals are fully ablated and thatany unablated or partially ablated tissues will not form reconnect as topropagate erratic rhythm signals. By giving such indications to thephysician (of which indicator 1322 is one example), the physician candecide whether the first ablation was sufficient or continue withsubsequent ablations.

The following clauses list non-limiting embodiments of the disclosure:

1. A method or use to treat a predetermined patient population forparoxysmal atrial fibrillation, the method or use comprising:

ablating tissue of one or more targeted pulmonary veins with one or moreof a plurality of the electrodes of an independently controlledmulti-electrode radiofrequency balloon catheter, the balloon cathetercomprising the plurality of electrodes for radiofrequency ablation thatare independently controllable;

determining a characteristic, based on ablation parameters of theballoon catheter, of single shot pulmonary vein isolation (PVI) successrate; and

achieving, based on the characteristic and step of ablating tissue, asingle shot isolation PVI success rate in the isolation of all targetedpulmonary veins for the predetermined patient population.

2. The method or use of clause 1, wherein the step of achieving thesingle shot isolation PVI success rate further comprises furtherablating tissue of one or more targeted pulmonary veins, based on thecharacteristic, with one or more of a plurality of the electrodes.

3. The method or use of clause 1, wherein the step of achieving thesingle shot isolation PVI success rate further comprises ceasing furthertissue ablation with the multi-electrode radiofrequency ballooncatheter, based on the characteristic.

4. The method or use of clause 1, wherein the step of achieving thesingle shot isolation PVI success rate further comprises achieving atleast about a 91.7% success rate by ablating with a pre-ablation meaninitial impedance of less than about 95Ω.

5. The method or use of clause 1, wherein the step of achieving thesingle shot isolation PVI success rate further comprises achieving atleast about a 91.7% success rate by ablating with a pre-ablation highestinitial impedance of less than about 100Ω.

6. The method or use of clause 1, wherein the step of achieving thesingle shot isolation PVI success rate further comprises achieving atleast about 87% success rate by ablating with a pre-ablation initialanterior wall impedance of less than about 95Ω.

7. The method or use of clause 1, wherein the step of achieving thesingle shot isolation PVI success rate further comprises achieving atleast about 85% success rate by ablating with a pre-ablation lowestinitial anterior wall impedance of between about 80-90Ω.

8. The method or use of clause 1, wherein the step of achieving thesingle shot isolation PVI success rate further comprises achieving atleast about 88% success rate by ablating with a pre-ablation highestinitial anterior wall impedance of about 110Ω.

9. The method or use of clause 1, wherein the step of achieving thesingle shot isolation PVI success rate further comprises achieving atleast about 87.5% success rate by ablating with a pre-ablation initialanterior wall impedance variation impedance range of less than about20Ω.

10. The method or use of clause 1, wherein the characteristic is apredictor of the single shot isolation PVI success rate before ablationwas limiting a highest initial temperature to less than about 31° C.among the electrodes of the balloon catheter.

11. The method or use of clause 1, wherein the characteristic is apredictor of the single shot isolation PVI success rate before ablationwas permitting a lowest anterior wall impedance between approximatelyabout 80-90Ω.

12. The method or use of clause 1, wherein the step of achieving thesingle shot isolation PVI success rate further comprises achieving atleast about a 90% success rate by ablating with a mean initial impedanceof less than about 95Ω for and a highest initial impedance of less thanabout 110Ω.

13. The method or use of clause 1, wherein the characteristic is apredictor is of the single shot isolation PVI success rate beforeablation, the predictor being initial temperature and impedance at alesion site just before the step of ablating.

14. The method or use of clause 1, wherein the characteristic is apredictor is of the single shot isolation PVI success rate beforeablation, the predictor being relatively low initial temperature andimpedance at a lesion site just before the step of ablating.

15. The method or use of clause 1, wherein the characteristic is apredictor is of the single shot isolation PVI success rate beforeablation, the predictor being initial temperature in a relatively lowrange and impedance at a lesion site just before the step of ablating.

16. The method or use of clause 1, wherein the characteristic is apredictor is of the single shot isolation PVI success rate beforeablation, the predictor being initial impedance impedance havingrelatively high values with a relatively narrow range.

17. The method or use of clause 1, wherein the characteristic is apredictor is of the single shot isolation PVI success rate beforeablation, the predictor being absolute values of impedance readingswithin a predetermined range.

18. The method or use of clause 1, wherein the characteristic is apredictor is of the single shot isolation PVI success rate before andduring ablation, the predictor being electrode temperature before andduring ablation.

19. The method or use of clause 1, wherein the characteristic is apredictor is of the single shot isolation PVI success rate beforeablation, the predictor being mean initial temperature, and wherein themean initial temperature is approximately less than about 28° C. and thesingle shot isolation PVI success rate is at least approximately about90%.

20. The method or use of clause 1, wherein the characteristic is apredictor is of the single shot isolation PVI success rate beforeablation, the predictor being a distributed initial temperature, andwherein the distributed initial temperature is approximately greaterthan about 31° C., and the single shot isolation PVI success rate is atleast approximately about 90%.

21. The method or use of clause 1, wherein the characteristic is apredictor is of the single shot isolation PVI success rate beforeablation, the predictor being a distributed initial temperature, andwherein the distributed initial temperature is approximately greaterthan about 30° C., and the single shot isolation PVI success rate is atleast approximately about 90%.

22. The method or use of clause 1, wherein the characteristic is apredictor is of the single shot isolation PVI success rate beforeablation, the predictor being a distributed initial temperature, andwherein the distributed initial temperature is approximately greaterthan about 29° C., and the single shot isolation PVI success rate is atleast approximately about 90%.

23. The method or use of clause 1, wherein the characteristic is apredictor is of the single shot isolation PVI success rate beforeablation, the predictor being a pre-ablation lowest temperature slope,and wherein the pre-ablation lowest temperature slope is approximatelygreater than about 0.75° C./sec, and the single shot isolation PVIsuccess rate is at least approximately about 90%.

24. The method or use of clause 1, wherein the characteristic is apredictor is of the single shot isolation PVI success rate beforeablation, the predictor being a pre-ablation lowest value temperature,and wherein the pre-ablation lowest value temperature is approximatelygreater than about 6° C., and the single shot isolation PVI success rateis at least approximately about 90%.

25. The method or use of clause 1, wherein the characteristic is apredictor is of the single shot isolation PVI success rate beforeablation, the predictor being a pre-ablation highest initialtemperature, and wherein the pre-ablation highest initial temperature isapproximately less than about 31° C., and the single shot isolation PVIsuccess rate is at least approximately about 90%.

26. The method or use of clause 1, wherein the characteristic is apredictor is of the single shot isolation PVI success rate beforeablation, the predictor being a pre-ablation initial temperaturevariation, and wherein the pre-ablation initial temperature variation isapproximately less than about 3° C., and the single shot isolation PVIsuccess rate is at least approximately about 95%.

27. The method or use of clause 1, wherein the characteristic is apredictor is of the single shot isolation PVI success rate beforeablation, the predictor being a pre-ablation initial impedancevariation, and wherein the pre-ablation initial impedance variationcomprises an optimal range of approximately less than about 20Ω, and thesingle shot isolation PVI success rate is at least approximately about88.5%.

28. The method or use of clause 1, wherein the characteristic is apredictor is of the single shot isolation PVI success rate beforeablation, the predictor being a pre-ablation lowest value impedancedrop, and wherein the pre-ablation lowest value impedance drop isapproximately greater than about 12Ω, and the single shot isolation PVIsuccess rate is at least approximately about 90%.

29. The method or use of clause 1, wherein the characteristic is apredictor is of the single shot isolation PVI success rate beforeablation, the predictor being a pre-ablation impedance drop variation,and wherein the pre-ablation impedance drop variation is approximatelygreater than about 20Ω, and the single shot isolation PVI success rateis at least approximately about 85%.

30. The method or use of clause 1, wherein the characteristic is apredictor is of the single shot isolation PVI success rate beforeablation, the predictor being a pre-ablation lowest value impedance droppercent, and wherein the pre-ablation lowest value impedance droppercent is greater than or equal to approximately about 12%, and thesingle shot isolation PVI success rate is at least approximately about90%.

31. The method or use of clause 1, wherein the characteristic is apredictor is of the single shot isolation PVI success rate beforeablation, the predictor being a pre-ablation impedance drop percentvariation, and wherein the pre-ablation impedance drop percent variationis less than about 20Ω, and the single shot isolation PVI success rateis at least approximately about 85%.

32. The method or use of clause 1, wherein when a number of electrodeswith initial impedance deviation from mean value is zero, the singleshot isolation PVI success rate is approximately about 92%.

33. The method or use of clause 1, wherein the characteristic is apredictor is of the single shot isolation PVI success rate beforeablation, the predictor being a difference of impedance between anteriorand posterior wall.

34. The method or use of clause 33, wherein the difference is less thanapproximately about 20Ω and the single-shot PVI success rate is at leastapproximately about 85% for the predetermined patient population.

35. The method or use of clause 33, wherein the difference is less thanapproximately about 20Ω and the single-shot PVI success rate is at leastapproximately about 85% for the predetermined patient population of atleast 25 patients.

36. The method or use of clause 33, wherein the difference isapproximately between 20 to 30Ω and the single-shot PVI success rate isat least approximately about 78% for the predetermined patientpopulation.

37. The method or use of clause 33, wherein the difference isapproximately between 20 to 30Ω and the single-shot PVI success rate isat least approximately about 78% for the predetermined patientpopulation of at least 75 patients.

38. The method or use of clause 33, wherein the difference isapproximately between 30 to 40Ω and the single-shot PVI success rate isat least approximately about 75% for the predetermined patientpopulation.

39. The method or use of clause 33, wherein the difference isapproximately between 30 to 40Ω and the single-shot PVI success rate isat least approximately about 75% for the predetermined patientpopulation of at least 60 patients.

40. The method or use of clause 33, wherein the difference isapproximately between 40 to 50Ω and the single-shot PVI success rate isat least approximately about 67% for the predetermined patientpopulation.

41. The method or use of clause 33, wherein the difference isapproximately between 40 to 50Ω and the single-shot PVI success rate isat least approximately about 67% for a predetermined patient populationof at least 34 patients.

42. The method or use of clause 33, wherein the difference isapproximately between 50 to 60Ω and the single-shot PVI success rate isat least approximately about 35% for the predetermined patientpopulation.

43. The method or use of clause 33, wherein the difference isapproximately between 50 to 60Ω and the single-shot PVI success rate isat least approximately about 35% for the predetermined patientpopulation of at least 11 patients.

44. The method or use of clause 33, wherein the difference is greaterthan approximately about 60Ω and the single-shot PVI success rate is atleast approximately about 33% for the pre-determined patient population.

45. The method or use of clause 33, wherein the difference is greaterthan approximately about 60Ω and the single-shot PVI success rate is atleast approximately about 33% for the pre-determined patient populationof at least 9 patients.

46. The method or use of clause 33, wherein the balloon catheter is afull-circle all electrode burning ablation catheter.

47. The method or use of clause 33, wherein the step of ablating tissueis for a duration of 60 seconds.

48. The method or use of clause 1, wherein the characteristic is apredictor is of the single shot isolation PVI success rate beforeablation, and wherein pre-ablation mean initial impedance is thepredictor.

49. The method or use of clause 1, wherein the characteristic is apredictor is of the single shot isolation PVI success rate beforeablation, and wherein pre-ablation initial impedance variation is thepredictor.

50. The method or use of clause 1, wherein the characteristic is anevaluator of the single shot isolation PVI success rate post ablation,and wherein post-ablation lowest impedance drop is the evaluator.

51. The method or use of clause 1, wherein the characteristic is anevaluator of the single shot isolation PVI success rate post ablation,and wherein post-ablation impedance drop variation is the evaluator.

52. The method or use of clause 1, wherein the characteristic is apredictor is of the single shot isolation PVI success rate beforeablation, and wherein post-ablation mean temperature slope is theevaluator.

53. The method or use of clause 1, wherein the characteristic is anevaluator of the single shot isolation PVI success rate post ablation,and wherein post-ablation lowest temperature slope is the predictor.

54. The method or use of clause 1, wherein the characteristic is anevaluator of the single shot isolation PVI success rate post ablation,and wherein post-ablation mean temperature rise is the evaluator.

55. The method or use of clause 1, wherein the characteristic is anevaluator of the single shot isolation PVI success rate post ablation,and wherein post-ablation lowest temperature rise is the evaluator.

56. The method or use of clause 1, wherein the characteristic is anevaluator of the single shot isolation PVI success rate post ablation,and wherein post-ablation lowest impedance drop percentage is theevaluator.

57. The method or use of clause 1, wherein the characteristic is anevaluator of the single shot isolation PVI success rate post ablation,and wherein post-ablation variation of impedance drop percentage is theevaluator.

58. The method or use of clause 1, wherein the characteristic is apredictor is of the single shot isolation PVI success rate beforeablation, and wherein pre-ablation lowest impedance drop is thepredictor.

59. The method or use of clause 1, wherein the characteristic is apredictor is of the single shot isolation PVI success rate beforeablation, and wherein pre-ablation initial temperature variation is thepredictor.

60. The method or use of clause 1, wherein the characteristic is apredictor is of the single shot isolation PVI success rate beforeablation, and wherein pre-ablation maximum initial impedance is thepredictor.

61. The method or use of clause 1, wherein the characteristic is apredictor is of the single shot isolation PVI success rate beforeablation, and wherein pre-ablation mean initial anterior wall impedanceis the predictor.

62. The method or use of clause 1, wherein the characteristic is apredictor is of the single shot isolation PVI success rate beforeablation, and wherein pre-ablation lowest anterior wall impedance is thepredictor.

63. The method or use of clause 1, wherein the characteristic is apredictor is of the single shot isolation PVI success rate beforeablation, and wherein pre-ablation maximum anterior wall impedance isthe predictor.

64. The method or use of clause 1, wherein the characteristic is apredictor is of the single shot isolation PVI success rate beforeablation, and wherein pre-ablation anterior wall impedance variation isthe predictor.

65. The method or use of any preceding clause, wherein impedance valueswere among the electrodes of an anterior wall.

66. The method or use of any preceding clause, wherein thecharacteristic is a predictor is of the single shot isolation PVIsuccess rate before ablation, and wherein the predictor is determinedby:

${Probability}\text{∼}\frac{e^{Y}}{( {1 + e^{Y}} )}$Y∼4.367 − 0.420 Δ T₀ − 0.0486 Δ Z₀

wherein ΔT₀ is initial impedance variation and ΔZ₀ is initialtemperature variation.

67. The method or use of any preceding clause, wherein thecharacteristic is a predictor is of the single shot isolation PVIsuccess rate before ablation, and wherein the predictor is determinedby:

${Prob}\text{∼}\frac{e^{Y}}{( {1 + e^{Y}} )}$Y∼26.78 − 0.576T_(0max ) − 0.0632 Z_(0max )

wherein T_(0max) is highest initial temperature and Z_(0max) is highestinitial impedance.

68. The method or use of any preceding clause, wherein thecharacteristic is a predictor is of the single shot isolation PVIsuccess rate before ablation, and wherein the predictor is determinedby:

${Prob}\text{∼}\frac{e^{Y}}{( {1 + e^{Y}} )}$Y∼27.70 − 0.540 T_(0max ) − 0.0959 Z_(0max )

wherein T_(0max) is highest initial temperature and Z_(0max) is highestinitial impedance.

69. The method or use of any preceding clause, wherein thecharacteristic is a predictor is of the single shot isolation PVIsuccess rate before ablation, and wherein the predictor is determinedby:

${Prob}\text{∼}\frac{e^{Y}}{( {1 + e^{Y}} )}$Y∼9.31 − 0.408 Δ T₀ − 0.0544 Z_(0max )

wherein ΔT₀ is initial temperature variation and Z_(0max) is highestinitial impedance.

70. The method or use of any preceding clause, wherein thecharacteristic is a predictor is of the single shot isolation PVIsuccess rate before ablation, and wherein the predictor is determinedby:

${Prob}\text{∼}\frac{e^{Y}}{( {1 + e^{Y}} )}$Y∼22.61 − 0.622T_(0max ) − 0.0626 Δ Z₀

wherein T_(0max) is highest initial temperature and ΔZ₀ is initialimpedance variation.

71. The method or use of any preceding clause, wherein thecharacteristic is a predictor is of the single shot isolation PVIsuccess rate before ablation, and wherein the predictor is determinedby:

${Prob}\text{∼}\frac{e^{Y}}{( {1 + e^{Y}} )}$Y∼11.53 − 0.439 Δ T₀ − 0.0856 Z_(0mean)

wherein ΔT₀ is initial temperature variation and Z_(0max) is meaninitial impedance.

72. The method or use of any preceding clause, wherein thecharacteristic is a predictor is of the single shot isolation PVIsuccess rate before ablation, and wherein the predictor is determinedby:

${Prob}\text{∼}\frac{e^{Y}}{( {1 + e^{Y}} )}$Y∼26.52 + 0.013 Δ T₀ − 0.594 T_(0max ) − 0.0122 Δ Z₀ − 0.053 Z_(0max )

wherein ΔT₀ is initial temperature variation, T_(0max) is highestinitial temperature, ΔZ₀ is initial impedance variation, and Z_(0max) ishighest initial impedance.

73. The method or use of any preceding clause, wherein thecharacteristic is an evaluator of the single shot isolation PVI successrate post ablation, and wherein the evaluator is determined by:

${Prob}\text{∼}\frac{e^{Y}}{( {1 + e^{Y}} )}$Y∼1.562 + 0.2856 Δ T_(min) − 0.0629 ΔZ_(drop)

wherein ΔT_(min) is lowest temperature rise and ΔZ_(drop) is impedancedrop variation.

74. The method or use of any preceding clause, wherein thecharacteristic is an evaluator of the single shot isolation PVI successrate post ablation, and wherein the evaluator is determined by:

$P\text{∼}\frac{e^{Y}}{( {1 + e^{Y}} )}$Y∼ − 0.507 + 0.206 Δ T_(min) + 0.083 Z_(dropmin)

wherein ΔT_(min) is lowest temperature rise and Z_(dropmin) is minimumimpedance drop.

75. The method or use of any preceding clause, wherein thecharacteristic is an evaluator of the single shot isolation PVI successrate post ablation, and wherein the evaluator is determined by:

$P\text{∼}\frac{e^{Y}}{( {1 + e^{Y}} )}$Y∼1.248 + 0.2486 Δ T_(min) − 0.0594 Δ Z_(drop) + 0.0419 Z_(dropmin)

wherein ΔT_(min) is lowest temperature rise and Z_(dropmin) is minimumimpedance drop.

76. The method or use of any preceding clause, wherein thecharacteristic is an evaluator of the single shot isolation PVI successrate post ablation, and wherein the evaluator is determined by:

$P\text{∼}\frac{e^{Y}}{( {1 + e^{Y}} )}$Y∼1.174 + 0.2515Δ T_(min) − 0.0564Δ Z_(drop)  %

wherein ΔT_(min) is lowest temperature rise and Δ Z_(drop) is impedancedrop percent variation.

77. The method or use of any preceding clause, wherein thecharacteristic is an evaluator of the single shot isolation PVI successrate post ablation, and wherein the evaluator is determined by:

$P \sim \frac{e^{Y}}{( {1 + e^{Y}} )}$Y ∼ −0.644 + 0.170 Δ T_(min) + 0.107 Z_(drop)%_(min)

wherein ΔT_(min) is lowest temperature rise and Z_(drop)%_(min) islowest impedance drop percent.

78. The method or use of any preceding clause, wherein thecharacteristic is an evaluator of the single shot isolation PVI successrate post ablation, and wherein the evaluator is determined by:

$P \sim \frac{e^{Y}}{( {1 + e^{Y}} )}$Y ∼ 0.339 + 0.187 Δ T_(min) + 0.0737 Z_(drop)%_(min) − 0.0368 Δ Z_(drop)%

wherein ΔT_(min) is lowest temperature rise, Z_(drop)%_(min) is lowestimpedance drop percent, and Δ Z_(drop)%) is impedance drop percentvariation.

79. The method or use of any preceding clause, wherein thecharacteristic is an evaluator of the single shot isolation PVI successrate post ablation, and wherein the evaluator is determined by:

$P \sim \frac{e^{Y}}{( {1 + e^{Y}} )}$Y ∼ 1.043 + 0.777 T_(min)^(′) + 0.171 ΔT_(min) + 0.0479 Z_(drop − min ) − 0.0589 Δ Z_(drop)

wherein T′_(min) is lowest temperature slope, ΔT_(min) is lowesttemperature rise, Z_(drop)-min is lowest impedance drop and ΔZ_(drop) isimpedance drop variation.

80. The method or use of claim 1, further comprising the step ofdisplaying a graphical representation of the independently controllableelectrodes and the ablation parameters.

81. The method or use of clause 74, wherein one ablation parametercomprises impedance measured proximate each electrode.

82. The method or use of clause 75, wherein the measured impedancecomprises impedance measured before ablation.

83. The method or use of clause 75, wherein the measured impedancecomprises impedance measured after ablation.

84. The method or use of clause 75, wherein the measured impedancecomprises impedance measured before and impedance measured afterablation.

85. The method or use of clause 74, wherein one ablation parametercomprises temperature measured proximate each electrode.

86. The method or use of clause 74, wherein one ablation parametercomprises a maximum temperature measured proximate each electrode duringthe ablating.

87. The method or use of clause 74, wherein one ablation parametercomprises a measured temperature rise from a beginning of ablating to anend of the ablating.

88. A method or use to treat a plurality of patients for paroxysmalatrial fibrillation, the method or use comprising the steps of:

delivering a multi-electrode radiofrequency balloon catheter having aplurality of independently controllable electrodes for radiofrequencyablation and a multi-electrode diagnostic catheter to one or moretargeted pulmonary veins;

ablating tissue of the one or more targeted pulmonary veins with one ormore of the plurality of the electrodes independently controlledmulti-electrode radiofrequency balloon catheter;

diagnosing the one or more targeted pulmonary veins using themulti-electrode diagnostic catheter; and

achieving at least one of a predetermined clinical effectiveness andacute effectiveness of the multi-electrode radiofrequency ballooncatheter and the multi-electrode diagnostic catheter in the isolation ofthe one or more targeted pulmonary veins, during and approximately 3months after the ablating step.

89. The method or use of clause 82, wherein acute effectiveness isdefined by confirming if there is an entrance block in all targetedpulmonary veins after adenosine and/or isoproterenol challenge.

90. The method or use of clause 83, further comprising: determining theacute effectiveness determined at approximately 3 months after theablating step; and generating an estimated acute effectiveness atapproximately 12 months after the ablating step based on the acuteeffectiveness determined at approximately 3 months.

91. The method or use of clause 84, wherein the estimated acuteeffectiveness at approximately 12 months is substantially similar to theacute effectiveness determined at approximately 3 months.

92. The method or use of clause 83, wherein the acute effectiveness isfurther defined by success greater than 90% for the plurality ofpatients.

93. The method or use of clause 83, wherein the acute effectiveness isfurther defined by success greater than 95% for the plurality ofpatients.

94. The method or use of clause 83, wherein a Type-1 error rate forpower the acute effectiveness and the clinical effectiveness of alltargeted veins are controlled at approximately a 5% level, the method oruse further comprising:

determining whether the ablating is clinically successful for theplurality of patients if both the acute effectiveness and the clinicaleffectiveness indications are controlled at approximately the 5% level.

95. The method or use of clause 83, wherein the acute effectiveness isat least 80% for the plurality of patients being at least 80 patients.

96. The method or use of clause 83, wherein the acute effectiveness isat least 80% for the plurality of patients being at least 130 patients.

97. The method or use of clause 83, wherein the acute effectiveness isat least 80% for the plurality of patients being at least 180 patients.

98. The method or use of clause 83, wherein the acute effectiveness isat least 80% for the plurality of patients being at least 230 patients.

99. The method or use of clause 83, wherein the acute effectiveness isfurther defined by confirming if there is an entrance block in alltargeted pulmonary veins after adenosine and/or isoproterenol challengeusing a focal ablation catheter.

100. The method or use of clause 83, wherein the acute effectiveness isfurther defined by confirming if there is an entrance block in alltargeted pulmonary veins after adenosine and/or isoproterenol challengewithout using a focal ablation catheter.

101. The method or use of clause 82, wherein the ablating isadministered on the plurality of patients diagnosed with symptomaticparoxysmal atrial fibrillation.

102. The method or use of clause 82, wherein the step of diagnosingfurther comprises:

electrophysiological mapping of the heart.

103. The method or use of clause 82, wherein the multi-electrodediagnostic catheter further comprises a high torque shaft with ahalo-shaped tip section containing a plurality of pairs of electrodesvisible under fluoroscopy.

104. The method or use of clause 82, wherein the plurality of patientsis at least 80.

105. The method or use of clause 82, wherein the plurality of patientsis at least 130.

106. The method or use of clause 82, wherein the plurality of patientsis at least 180.

107. The method or use of clause 82, wherein the plurality of patientsis at least 230.

108. The method or use of clause 82, wherein the predetermined acuteeffectiveness is de-fined by ulceration being absent in the plurality ofpatients after the ablating.

109. The method or use of clause 82, wherein the predetermined acuteeffectiveness is de-fined by a complication rate of approximately 13% orfewer of the plurality of patients experiencing esophageal erythemaafter the ablating.

110. The method or use of clause 82, wherein the predetermined acuteeffectiveness is de-fined by a complication rate of approximately 25% orfewer of the plurality of patients experiencing new asymptomaticcerebral embolic lesions after the ablating.

111. The method or use of clause 82, wherein the predetermined acuteeffectiveness is de-fined by a complication rate of approximately 20% orfewer of the plurality of patients experiencing new asymptomaticcerebral embolic lesions after the ablating.

112. The method or use of clause 82, wherein the predetermined acuteeffectiveness is de-fined by a complication rate of approximately 5-9%or fewer of the plurality of patients experiencing a primary adverseevent by approximately 7 or more days after the ablating.

113. The method or use of clause 82, wherein inclusion criteria for theplurality of patients comprises:

a diagnosis with symptomatic paroxysmal atrial fibrillation; and

a patient capability to comply with uninterrupted per-protocolanticoagulation requirements.

114. The method or use of clause 82, wherein the predetermined acuteeffectiveness is de-fined by a total procedure time.

115. The method or use of clause 82, wherein the predetermined acuteeffectiveness is de-fined by a total ablation time.

116. The method or use of clause 82, wherein the predetermined acuteeffectiveness is de-fined by a total RF application time.

117. The method or use of clause 82, wherein the predetermined acuteeffectiveness is de-fined by a total dwell time of the multi-electroderadiofrequency balloon catheter.

118. The method or use of clause 82, wherein the predetermined acuteeffectiveness is de-fined by a total time to isolate all targetedpulmonary veins.

119. The method or use of clause 82, wherein the predetermined acuteeffectiveness is de-fined by a number and a total time of applicationsby the multi-electrode radiofrequency balloon catheter per location ofall targeted pulmonary veins.

120. The method or use of clause 82, wherein the predetermined acuteeffectiveness is de-fined by a number and a total time of applicationsby the multi-electrode radiofrequency balloon catheter per patient.

121. The method or use of clause 82, wherein the predetermined acuteeffectiveness is de-fined by a number and a total time of applicationsby the multi-electrode radiofrequency balloon catheter per targetedvein.

122. The method or use of any previous clause, wherein themulti-electrode radiofrequency balloon catheter comprises:

a compliant balloon with a plurality of electrodes bonded configured todeliver RF energy to tissue of the pulmonary vein and sense temperatureat each electrode.

123. The method or use of clause 82, wherein clinical effectiveness isdefined by an incidence of early onset of one or more adverse eventswithin a predetermined time of the method or use being implemented.

124. The method or use of clause 117, wherein the predetermined time isat least 7 days.

125. The method or use of clause 117, wherein the one or more adverseevents comprise: death, atrioesophageal fistula, myocardial infarction,cardiac tamponade/perforation, thromboembolism, stroke, TIA (TransientIschemic Attack), phrenic nerve paralysis, pulmonary vein stenosis, andthe major vascular access bleeding.

126. The method or use of clause 117, wherein the one or more adverseevents comprise: incidence of individual adverse events from a primarycomposite; incidence of serious adverse de-vice effect; incidence ofserious adverse events within 7 days, at least 7¬30 days, and at least30 days following the ablating; incidence of non-serious adverse events;incidence of pre- and post-ablation asymptomatic and symptomaticcerebral emboli as determined by MRI evaluation; and frequency, anatomiclocation, and size (diameter and volume) of cerebral emboli by MRIevaluations at baseline, post-ablation and during follow-up.

127. The method or use of clause 117, wherein the one or more adverseevents for approximately 5-9% of the plurality of patients, the one ormore adverse events comprising:

NIHSS (National Institute of Health Stroke Scale) scores at baseline,post-ablation and during follow-up;

a summary of MoCA (Montreal Cognitive Assessment) and mRS (ModifiedRanking Scale) scores at baseline, 1 month and during further follow-up;a rate of hospitalization for cardiovascular events; a percentage (%) ofpulmonary vein isolation touch-up by focal catheter among the one ormore targeted veins;

a percentage (%) of subjects with use of focal catheter ablations fornon-PV triggers;

a percentage (%) of subjects with freedom from documented symptomaticatrial fibrillation (AF), atrial tachycardia (AT), or atypical (leftside) atrial flutter (AFL) episodes (episodes >30 seconds on arrhythmiamonitoring device from day 91 to 180);

a percentage (%) of subjects with freedom from documented atrialfibrillation (AF), atrial tachycardia (AT), or atypical (left side)atrial flutter (AFL);

one or more episodes that endure for 30 or more seconds on an arrhythmiamonitoring device from day 91 to 180 following the ablating; and

one or more procedural parameters including total procedure and ablationtime, balloon dwell time, RF application time, a number of RFapplications, fluoroscopy time and dose.

128. The method or use of clause 82, wherein the acute safety rateincludes complication rates of 10% or less and is defined by incidenceof asymptomatic cerebral embolic lesions at a discharge magneticresonance imaging (MRI).

129. The method or use of clause 82, wherein the acute effectivenessrate is 100% and is de-fined by electrically isolating all targetedpulmonary veins without use of a focal ablation catheter.

130. The method or use of clause 82, wherein the acute effectivenessrate is defined by a freedom from documented atrial fibrillation, atrialtachycardia, or atypical atrial flutter episodes based onelectrocardiographic data through an effectiveness evaluation period (1year).

131. The method or use of clause 82, wherein the acute effectivenessrate is defined by pulmonary vein isolation touch-up by a focal catheteramong all targeted pulmonary veins.

132. The method or use of clause 82, wherein the predetermined clinicaleffectiveness rate is defined by 10% or less complication rates relatedto incidence of post-ablation symptomatic and asymptomatic cerebralemboli as compared to pre-ablation.

133. The method or use of clause 82, wherein the multi-electrodediagnostic catheter is con-figured for electrophysiological recordingand stimulation of the atrial region of the heart and is used inconjunction with the multi-electrode radiofrequency balloon catheter.

134. A method or use to treat a plurality of patients for paroxysmalatrial fibrillation, the method or use comprising the steps of:

delivering a multi-electrode radiofrequency balloon catheter having aplurality of independently controllable electrodes for radiofrequencyablation and a multi-electrode diagnostic catheter to one or moretargeted pulmonary veins; and

ablating tissue of one or more targeted pulmonary veins with one or moreof the plurality of the electrodes independently controlledmulti-electrode radiofrequency balloon catheter;

diagnosing all targeted pulmonary veins using the multi-electrodediagnostic catheter; and

achieving a predetermined rate of adverse events based on use of themulti-electrode radiofrequency balloon catheter and the multi-electrodediagnostic catheter in the isolation of all targeted pulmonary veins,during and approximately 6 months after the method or use.

135. A method or use to treat a plurality of patients for paroxysmalatrial fibrillation, the method or use comprising the steps of:

evaluating a number and size of all targeted pulmonary veins and anatomyof the left atrial;

puncturing the transseptal;

selectively positioning a multi-electrode esophageal temperaturemonitoring device in the vasculature with respect to all targetedpulmonary veins;

selectively positioning a multi-electrode radiofrequency ballooncatheter in the vasculature with respect to all targeted pulmonaryveins, the multi-electrode radiofrequency balloon catheter having aplurality of independently controllable electrodes for radiofrequencyablation;

selectively positioning a multi-electrode diagnostic catheter in thevasculature with respect to all targeted pulmonary veins;

ablating tissue of all targeted pulmonary veins with one or more of theplurality of the electrodes independently controlled multi-electroderadiofrequency balloon catheter;

confirming isolation of all targeted pulmonary veins using themulti-electrode diagnostic catheter;

confirming existence of an entrance block in all targeted pulmonaryveins;

achieving a predetermined clinical effectiveness and/or acuteeffectiveness of the method or use, based on the confirmed existence ofthe entrance block, regarding the isolation of all targeted pulmonaryveins following the method or use.

136. The method or use according to any of the preceding clauses,further comprising: map-ping all targeted pulmonary veins using thediagnostic catheter.

137. The method or use according to any of the preceding clauses,wherein exclusion criteria for the plurality of patients comprises atleast one of the following:

atrial fibrillation secondary to electrolyte imbalance, thyroid disease,or reversible or non-cardiac cause;

previous surgical or catheter ablation for atrial fibrillation;

anticipated to receive ablation outside all targeted pulmonary veinsostia and CTI region;

previously diagnosed with persistent, longstanding atrial fibrillationand/or continuous atrial fibrillation >7 days, or >48 hrs terminated bycardioversion;

any percutaneous coronary intervention (PCI) within the past 2 months;

valve repair or replacement and presence of a prosthetic valve;

any carotid stenting or endarterectomy;

coronary artery bypass grafting, cardiac surgery, valvular cardiacsurgical or percutaneous procedure within the past 6 months;

documented left atrium thrombus on baseline imaging;

LA antero posterior diameter greater than 50 mm;

any pulmonary vein with a diameter greater than or equal to 26 mm;

left ventricular ejection fraction less than 40%;

contraindication to anticoagulation;

history of blood clotting or bleeding abnormalities;

myocardial infarction within the past 2 months;

documented thromboembolic event within the past 12 months;

rheumatic heart disease;

awaiting cardiac transplantation or other cardiac surgery within thenext 12 months;

unstable angina;

acute illness or active systemic infection or sepsis;

diagnosed atrial myxoma or interatrial baffle or patch;

presence of implanted pacemaker, implantable cardioverter defibrillator,tissue-embedded, or iron-containing metal fragments;

significant pulmonary disease or any other disease or malfunction of thelungs or respiratory system that produces chronic symptoms;

significant congenital anomaly;

pregnancy or lactating;

enrollment in an investigational study evaluating another device,biologic, or drug;

pulmonary vein stenosis;

presence of intramural thrombus, tumor or other abnormality thatprecludes vascular access, or manipulation of the catheter;

presence of an IVC filter;

presence of a condition that precludes vascular access;

life expectancy or other disease processes likely to limit survival toless than 12 months;

contraindication to use of contrast agents for MRI;

presence of iron-containing metal fragments in the patient; or

unresolved pre-existing neurological deficit.

138. The method or use of any previous clause, wherein themulti-electrode radiofrequency balloon catheter comprises:

a compliant balloon with a plurality of electrodes configured to deliverRF energy to tissue of all targeted pulmonary veins and sensetemperature at each electrode.

139. The method or use of clause 132, wherein the plurality ofelectrodes is oriented circularly to circumferentially contact with anostia of the pulmonary vein.

140. The method or use of clause 132, further comprising using theplurality of electrodes for visualization, stimulation, recording, andablation.

141. The method or use of clause 132, wherein each electrode isconfigured so an amount of power delivered to each electrode iscontrolled independently.

142. The method or use of clause 132, wherein the multi-electroderadiofrequency balloon catheter further comprises a proximal handle, adistal tip, and a middle section disposed there-between.

143. The method or use of clause 136, wherein the proximal handle is adeflection thumb knob allowing for unidirectional deflection, a balloonadvancement mechanism, and a luer fitting for balloon inflation andirrigation.

144. The method or use of clause 132, wherein the multi-electroderadiofrequency balloon catheter further comprises

a high-torque shaft configured to be rotated to facilitate accuratepositioning of the catheter tip to a desired; and

a unidirectional braided deflectable tip section.

145. The method or use of any preceding clause, further comprising:

controlling irrigation to the multi-electrode radiofrequency ballooncatheter with an irrigation pump.

146. The method or use of any preceding clause, further comprising:

administering uninterrupted anticoagulation therapy at least 1 monthprior to the procedure.

147. The method or use of any preceding clause, wherein if the patientis receiving warfarin/coumadin therapy, the patient must have aninternational normalized ratio (INR)≥2 for at least 3 weeks prior to theprocedure.

148. The method or use of any preceding clause, wherein if the patientis receiving warfarin/coumadin therapy, the patient must be confirmed tohave an international normalized ratio (INR)≥2 within 48 hourspre-procedure.

149. The method or use of any preceding clause, further comprising:continuing anticoagulation therapy prior to the procedure.

150. The method or use of any preceding clause, further comprising:

administering a transseptal puncture;

confirming an activated clotting time target of ≥350 sec. prior toinserting the multi-electrode radiofrequency balloon catheter into theleft atrium and maintaining throughout the procedure;

introducing the multi-electrode radiofrequency balloon catheter;

introducing of a multi-electrode circular diagnostic catheter;

ablating the pulmonary vein with the multi-electrode radiofrequencyballoon catheter; determining in real time pulmonary vein isolation withthe multi-electrode circular diagnostic catheter; and

confirming whether an entrance is blocked in the pulmonary vein.

151. The method or use of any preceding clause, wherein themulti-electrode circular diagnostic catheter comprises:

an elongated body having a longitudinal axis;

a distal assembly distal the elongated body, the distal assembly havinga helical form comprising a proximal loop and a distal loop, and ashape-memory support member extending through at least the proximalloop, the proximal loop and the distal loop being oriented obliquely atan angle relative to the longitudinal axis of the elongated body;

at least one irrigated ablation ring electrode mounted on the proximalloop;

a control handle proximal the elongated body; and

a contraction wire having a proximal end in the control handle and adistal end anchored in the proximal loop, the control handle including afirst control member configured to actuate the contraction wire tocontract the proximal loop,

wherein the proximal loop has a first flexibility and the distal loophas a second flexibility, and the second flexibility is greater than thefirst flexibility.

152. A method or use of treating a plurality of patients for paroxysmalatrial fibrillation by applying energy to tissue of a subject's heartproximate to an esophagus, phrenic nerve, or lung, the method or usecomprising the steps of:

achieving at least one of a predetermined clinical effectiveness andacute effectiveness of the procedure based on use of a multi-electroderadiofrequency balloon catheter and a multi-electrode diagnosticcatheter in the isolation of the one or more targeted pulmonary veinsby:

positioning an expandable member proximate to the left atrium, theexpandable member of the multi-electrode radiofrequency balloon catheterhaving a longitudinal axis and including a plurality of electrodesdisposed about the longitudinal axis, each electrode capable of beingenergized independently, the plurality of electrodes including a firstelectrode having a first radiopaque marker and a second electrode havinga second radiopaque marker different from the first radiopaque marker;

viewing an image of the expandable member as well as the first andsecond radiopaque markers in the left atrium;

determining an orientation of the first and second radiopaque markerswith respect to a

portion of the left atrium closest to the esophagus, phrenic nerve, orlung, of the subject;

moving one of the first and second radiopaque markers to a portion ofthe left atrium closest to the esophagus, phrenic nerve or lung;

energizing one or more electrodes indexed to the one of the radiopaquemarkers proximate the portion close to the esophagus, phrenic nerve, orlung, at a lower energization setting as compared to other electrodes tocreate a transmural lesion in the left atrium with little or no effectto adjacent anatomical structures; and

electrophysiologically recording and stimulating the atrial region ofthe tissue proximate to the esophagus, phrenic nerve, or lung using themulti-electrode diagnostic catheter.

153. A clinically effective device to treat atrial fibrillation in agroup of patients, the device comprising an end probe coupled to atubular member that extends along a longitudinal axis from a proximalportion to a distal portion, the end probe comprising:

a first expandable membrane coupled to the tubular member;

a plurality of electrodes disposed generally equiangularly about thelongitudinal axis on an outer surface of the first expandable membrane;

at least one wire connected each of the plurality of electrodes, the atleast one wire of each electrode extending from the first expandablemembrane toward the tubular member; and

a second expandable membrane that encapsulates a portion of the at leastone wire between the second expandable membrane and the first expandablemembrane; and

wherein the device is configured to achieve a predeterminedeffectiveness rate of pulmonary vein isolation in the group of patients.

154. A clinically effective device to administer a procedure for cardiacelectrophysiological ablation of pulmonary veins of the atria andtreatment of drug refractory recurrent symptomatic pulmonary atrialfibrillation, the device comprising:

an end probe coupled to a tubular member that extends along alongitudinal axis from a proximal portion to a distal portion, the endprobe comprising:

a first expandable membrane coupled to the tubular member;

a plurality of electrodes disposed generally equiangularly about thelongitudinal axis on an outer surface of the first expandable membrane;

at least one wire connected each of the plurality of electrodes, the atleast one wire of each electrode extending from the first expandablemembrane toward the tubular member; and

a second expandable membrane that encapsulates a portion of the at leastone wire between the second expandable membrane and the first expandablemembrane so that each of the plurality of electrodes is independentlycontrolled to achieve a predetermined effectiveness rate of pulmonaryvein isolation.

155. A clinically effective device to administer a procedure for cardiacelectrophysiological ablation of pulmonary veins of the atria andtreatment of drug refractory recurrent symptomatic pulmonary atrialfibrillation, the device comprising:

an end probe coupled to a tubular member that extends along alongitudinal axis from a proximal portion to a distal portion, the endprobe comprising:

a first expandable membrane coupled to the tubular member;

a plurality of electrodes disposed generally equiangularly about thelongitudinal axis on an outer surface of the first expandable membrane;

at least one wire connected each of the plurality of electrodes, the atleast one wire of each electrode extending from the first expandablemembrane toward the tubular member; and

a second expandable membrane that encapsulates a portion of the at leastone wire between the second expandable membrane and the first expandablemembrane so that each of the plurality of electrodes is independentlycontrolled to achieve pulmonary vein isolation and at least a 97% safetyendpoint within seven (7) days of successful pulmonary vein isolation.

156. A clinically effective device to administer a procedure for cardiacelectrophysiological ablation of pulmonary veins of the atria andtreatment of drug refractory recurrent symptomatic pulmonary atrialfibrillation, the device comprising:

an end probe coupled to a tubular member that extends along alongitudinal axis from a proximal portion to a distal portion, the endprobe comprising:

a first expandable membrane coupled to the tubular member;

a plurality of electrodes disposed generally equiangularly about thelongitudinal axis on an outer surface of the first expandable membrane;

at least one wire connected each of the plurality of electrodes, the atleast one wire of each electrode extending from the first expandablemembrane toward the tubular member; and

a second expandable membrane that encapsulates a portion of the at leastone wire between the second expandable membrane and the first expandablemembrane so that each of the plurality of electrodes is independentlycontrolled to achieve pulmonary vein isolation and at least a 90% safetyendpoint within seven (7) days of successful pulmonary vein isolation.

157. The device of one of the preceding clauses, wherein thepredetermined effectiveness rate includes complication rates of 10% orless and is defined by existence or non-existence of asymptomaticcerebral embolic lesions at a discharge magnetic resonance imaging(MRI).

158. The device of one of the preceding clauses, wherein thepredetermined effectiveness rate includes complication rates ofapproximately 0% and is defined by existence or non-existence ofesophageal injury erythema.

159. The device of one of the preceding clauses, wherein thepredetermined effectiveness rate is approximately 100% and is defined byelectrically isolating all targeted pulmonary veins without use of afocal ablation catheter.

160. The device of one of the preceding clauses, wherein thepredetermined effectiveness rate is defined by a freedom from documentedatrial fibrillation, atrial tachycardia, or atypical atrial flutterepisodes based on electrocardiographic data through an effectivenessevaluation period.

161. The device of Clause 1, wherein the effectiveness evaluation periodis approximately one year.

162. The device of one of the preceding clauses, wherein thepredetermined effectiveness rate is defined by pulmonary vein isolationtouch-up by a focal catheter among all targeted pulmonary veins.

163. The device of one of the preceding clauses, wherein thepredetermined effectiveness rate is defined by using focal catheterablation for non-PV triggers during the index procedure.

164. The device of one of the preceding clauses, wherein thepredetermined effectiveness rate comprises a long-term effectivenessrate.

165. The device of one of the preceding clauses, wherein thepredetermined effectiveness rate is defined by an average number ofRadio-Frequency applications per patient and Radio-Frequency timerequired to isolate all pulmonary veins.

166. The device of one of the preceding clauses, wherein thepredetermined effectiveness rate is defined by an average number ofRadio-Frequency applications per vein and Radio-Frequency time requiredto isolate common pulmonary veins.

167. The device of one of the preceding clauses, wherein thepredetermined effectiveness rate is defined by an average number ofRadio-Frequency applications per patient and Radio-Frequency timerequired to isolate common pulmonary veins.

168. The device of one of the preceding clauses, wherein thepredetermined effectiveness rate is defined by determining incidence ofcomplication rates being 10% or less of post-ablation symptomatic andasymptomatic cerebral emboli as compared to pre-ablation.

169. The device of one of the preceding clauses, wherein thepredetermined effectiveness rate is defined by evaluating a presence ofemboli-associated neurological deficits by at least one of NIHSS and mRSassessments.

170. The device of any previous clause, wherein the end probe isconfigured for use in catheter-based cardiac electrophysiologicalmapping of the atria.

171. The device of any previous clause, wherein the end probe isconfigured for cardiac ablation.

172. The device of any previous clause, wherein the end probe comprises:the plurality of electrodes bonded to the first expandable membrane andconfigured to deliver Radio-Frequency energy to tissue of the pulmonaryvein and sense temperature at each electrode.

173. The device of any previous clause, wherein the plurality ofelectrodes is oriented circularly to circumferentially contact with anostia of the pulmonary vein.

174. The device of any previous clause, wherein the device is furtherconfigured for using the plurality of electrodes for visualization,stimulation, recording, and ablation.

175. The device of any previous clause, wherein each electrode isconfigured so an amount of power delivered to each electrode iscontrolled independently.

176. The device of any previous clause, wherein the end probe furthercomprises a proximal handle, a distal tip, and a middle section disposedtherebetween.

177. The device of any previous clause, wherein the proximal handle is adeflection thumb knob allowing for unidirectional deflection, a balloonadvancement mechanism, and a luer fitting for balloon inflation andirrigation.

178. The device of any previous clause, wherein the end probe furthercomprises a high-torque shaft configured to be rotated to facilitateaccurate positioning of the catheter tip to a desired; and

a unidirectional braided deflectable tip section.

179. The device of any previous clause, wherein the end probe furthercomprises:

a first substrate disposed on the membrane, the first substrateincluding a first radiopaque marker of a first form disposed thereon;and

a second substrate disposed on the membrane, the second substrateincluding a second radiopaque marker of a second form disposed thereon,the second form being different from the first form.

180. The device of any previous clause, further comprising an irrigationpump to provide irrigation fluid to the first expandable membrane andout of the first expandable membrane.

181. The device of any preceding clause, wherein the effectivenessevaluation period is at least 91 days following a delivery of the endprobe to the pulmonary vein; and

ablation of tissue proximate the pulmonary vein with the end probe.

182. The device of any preceding clause, wherein the effectivenessevaluation period is less than or equal to one year following a deliveryof the end probe to the pulmonary vein; and

ablation of tissue proximate the pulmonary vein with the end probe.

183. The device of any previous clause, wherein the predeterminedsuccess rate is 60% for a population size of at least 40 patients.

184. The device of any previous clause, wherein a population size forthe predetermined success rate is at least 300 patients.

185. The device of any previous clause, wherein a population size forthe predetermined success rate is at least 200 patients.

186. The device of any previous clause, wherein a population size forthe predetermined success rate is at least 100 patients.

187. The device of any previous clause, wherein a population size forthe predetermined success rate is at least 50 patients.

188. The device of any previous clause, wherein the predeterminedsuccess rate is at least 60%.

189. The device of any previous clause, wherein the predeterminedsuccess rate is determined by evaluation of the patient 7 days followinga delivery of the end probe to the pulmonary vein and ablation of tissueproximate the pulmonary vein with the end probe.

190. The device of any previous clause, wherein the predeterminedsuccess rate is determined by evaluation of the patient 1 monthfollowing a delivery of the end probe to the pulmonary vein; andablation of tissue proximate the pulmonary vein with the end probe.

191. The device of any previous clause, wherein the predeterminedsuccess rate is determined by evaluation of the patient 6 monthsfollowing a delivery of the end probe to the pulmonary vein; andablation of tissue proximate the pulmonary vein with the end probe.

192. The device of any previous clause, wherein the predeterminedsuccess rate is determined by evaluation of the patient 12 monthsfollowing a delivery of the end probe to the pulmonary vein; andablation of tissue proximate the pulmonary vein with the end probe.

193. The device of any previous clause, wherein the predeterminedsuccess rate further comprises: confirmation of an entrance block in thepulmonary vein after at least one of adenosine and isoproterenolchallenge.

194. The device of any previous clause, wherein the patient suffering atleast one of the following events is deemed as unsuccessful pulmonaryvein isolation, including:

device or procedure related death;

atrio-esophageal fistula, myocardial infarction;

cardiac Tamponade/Perforation;

thromboembolism;

stroke/Cerebrovascular Accident (CVA);

transient Ischemic Attach (TIA);

phrenic Nerve Paralysis, Pulmonary Vein Stenosis;

pericarditis;

pulmonary Edema;

major Vascular Access Complication/Bleeding; and

hospitalization (initial or prolonged).

195. The device of any previous clause, wherein the patient suffering atleast one of the following events is deemed as unsuccessful pulmonaryvein isolation, comprising: acute procedural failure;

repeat ablation or surgical treatment for AF/AT/Atypical (left-side) AFLafter the blanking period (after day 90 post index procedure);

DC cardioversion for AF/AT/Atypical (left-side) AFL, continuousAF/AT/AFL on a standard 12-lead ECG even if the recording is less than30 seconds in duration (after day 90 post index procedure);

a new Class I and/or Class III AAD is prescribed for AF duringeffectiveness evaluation period (day 91-365 post index procedure) orprescribed during the blanking period and continued past 90 days;

a previously failed Class I and/or Class III AAD (failed at or beforescreening) is taken for AF at a greater dose than the highestineffective historical dose during the effectiveness evaluation period;and

amiodarone is prescribed post procedure.

196. The device any previous clause, wherein the safety endpoint isdefined by a patient suffering a primary adverse event.

197. The device of any previous clause, wherein at least one risk factorfor the patient is selected from the group consisting of:

at least three (3) symptomatic episodes of atrial fibrillation that lastlasting ≥1 minute within six (6) months before the device;

at least one (1) atrial fibrillation episode electrocardiographicallydocumented within twelve (12) months prior to enrollment, wherebyelectrocardiographic documentation can include, but is not limited to,electrocardiogram (ECG), Holter monitor, or telemetry strip;

failing at least one (1) Class I or Class III AAD as evidenced byrecurrent symptomatic atrial fibrillation or intolerable side effects tothe AAD;

age 18-75 years;

secondary to electrolyte imbalance;

thyroid disease;

reversible or non-cardiac cause; and

previous surgical or catheter ablation for atrial fibrillation.

198. The device of any previous clause, wherein the patient has at leastone risk factor selected from the group consisting of:

Patients known to require ablation outside the PV ostia and CTI region;

Previously diagnosed with persistent or long-standing persistent atrialfibrillation and/or Continuous atrial fibrillation 7 days following thedevice procedure;

any percutaneous coronary intervention within the past 2 months;

repair or replacement or presence of a prosthetic valve;

any carotid stenting or endarterectomy within the past 6 months;

Coronary artery bypass grafting, cardiac surgery or valvular cardiacsurgical procedure within the past 6 months;

Documented left atrium thrombus within 1 day prior to the deviceprocedure;

left atrium antero posterior diameter >50 mm;

Left Ventricular Ejection Fraction <40%;

Contraindication to anticoagulation;

History of blood clotting or bleeding abnormalities;

Myocardial infarction within the past 2 months;

Documented thromboembolic event (including transient ischemic attack)within the past 12 months;

Rheumatic Heart Disease;

Uncontrolled heart failure or New York Heart Association (NYHA) functionclass III or IV;

Awaiting cardiac transplantation or other cardiac surgery within thenext 12 months;

Unstable angina;

Acute illness or active systemic infection or sepsis;

Diagnosed atrial myxoma or presence of an interatrial baffle or patch;

Presence of implanted pacemaker or implantable cardioverterdefibrillator (ICD);

Significant pulmonary disease or any other disease or malfunction of thelungs or respiratory system that produces chronic symptoms;

Significant congenital anomaly;

women who are pregnant;

enrollment in an investigational study evaluating another device,biologic, or drug;

known pulmonary vein stenosis;

presence of intramural thrombus, tumor or other abnormality thatprecludes vascular access, or manipulation of the catheter;

presence of an inferior vena cava filter;

presence of a condition that precludes vascular access;

life expectancy or other disease processes likely to limit survival toless than 12 months;

presenting contra-indication for the devices; and

patient on amiodarone at any time during the past 3 months prior toenrollment.

199. The device of any previous clause, wherein if the patient isreceiving warfarin/coumadin therapy, the patient must have aninternational normalized ratio ≥2 for at least 3 weeks prior to theprocedure.

200. The device of any previous clause, wherein if the patient isreceiving warfarin/coumadin therapy, the patient must be confirmed to be≥2 within 48 hours pre-procedure.

201. The device of any previous clause, wherein anticoagulation therapyis provided prior to the procedure.

202. The device of any previous clause, wherein an activated clottingtime of 350-400 seconds is targeted prior to insertion of the catheterand throughout the procedure.

203. The device of any previous clause, wherein an activated clottingtime levels are checked every 15-30 minutes during the procedure toensure an activated clotting time target of 350-400 seconds.

204. The device of any previous clause, wherein the multi-electrodecircular diagnostic catheter comprises:

an elongated body having a longitudinal axis;

a distal assembly distal the elongated body, the distal assembly havinga helical form comprising a proximal loop and a distal loop, and ashape-memory support member extending through at least the proximalloop, the proximal loop and the distal loop being oriented obliquely atan angle relative to the longitudinal axis of the elongated body;

at least one irrigated ablation ring electrode mounted on the proximalloop;

a control handle proximal the elongated body; and

a contraction wire having a proximal end in the control handle and adistal end anchored in the proximal loop, the control handle including afirst control member configured to actuate the contraction wire tocontract the proximal loop,

wherein the proximal loop has a first flexibility and the distal loophas a second flexibility, and the second flexibility is greater than thefirst flexibility.

205. Use of an independently controlled multi-electrode radiofrequencyballoon catheter to treat a predetermined patient population forparoxysmal atrial fibrillation, comprising:

ablating tissue of one or more targeted pulmonary veins with one or moreof a plurality of the electrodes of the independently controlledmulti-electrode radiofrequency balloon catheter, the balloon cathetercomprising the plurality of electrodes for radiofrequency ablation thatare independently controllable;

determining a characteristic, based on ablation parameters of theballoon catheter, of single shot pulmonary vein isolation (PVI) successrate; and

achieving, based on the characteristic and step of ablating tissue, asingle shot isolation PVI success rate in the isolation of all targetedpulmonary veins for the predetermined patient population.

206. Use according to Clause 205, wherein the step of achieving thesingle shot isolation PVI success rate further comprises furtherablating tissue of one or more targeted pulmonary veins, based on thecharacteristic, with one or more of a plurality of the electrodes.

207. Use according to Clause 205, wherein the step of achieving thesingle shot isolation PVI success rate further comprises ceasing furthertissue ablation with the multi-electrode radiofrequency ballooncatheter, based on the characteristic.

208. Use according to Clause 205, wherein the step of achieving thesingle shot isolation PVI success rate further comprises achieving atleast about a 91.7% success rate by ablating with a pre-ablation meaninitial impedance of less than about 95Ω.

209. Use according to Clause 205, wherein the step of achieving thesingle shot isolation PVI success rate further comprises achieving atleast about a 91.7% success rate by ablating with a pre-ablation highestinitial impedance of less than about 100Ω.

210. Use according to Clause 205, wherein the step of achieving thesingle shot isolation PVI success rate further comprises achieving atleast about 87% success rate by ablating with a pre-ablation initialanterior wall impedance of less than about 95Ω.

211. Use according to Clause 205, wherein the step of achieving thesingle shot isolation PVI success rate further comprises achieving atleast about 85% success rate by ablating with a pre-ablation lowestinitial anterior wall impedance of between about 80-90Ω.

212. Use according to Clause 205, wherein the step of achieving thesingle shot isolation PVI success rate further comprises achieving atleast about 88% success rate by ablating with a pre-ablation highestinitial anterior wall impedance of about 110Ω.

213. Use according to Clause 205, wherein the step of achieving thesingle shot isolation PVI success rate further comprises achieving atleast about 87.5% success rate by ablating with a pre-ablation initialanterior wall impedance variation impedance range of less than about20Ω.

214. Use according to Clause 205, wherein the characteristic is apredictor of the single shot isolation PVI success rate before ablationwas limiting a highest initial temperature to less than about 31° C.among the electrodes of the balloon catheter.

215. Use according to Clause 205, wherein the characteristic is apredictor of the single shot isolation PVI success rate before ablationwas permitting a lowest anterior wall impedance between approximatelyabout 80-90Ω.

216. Use according to Clause 205, wherein the step of achieving thesingle shot isolation PVI success rate further comprises achieving atleast about a 90% success rate by ablating with a mean initial impedanceof less than about 95Ω for and a highest initial impedance of less thanabout 110Ω.

217. Use according to Clause 205, wherein the characteristic is apredictor is of the single shot isolation PVI success rate beforeablation, the predictor being mean initial temperature, and wherein themean initial temperature is approximately less than about 28° C. and thesingle shot isolation PVI success rate is at least approximately about90%.

218. Use according to Clause 205, wherein the characteristic is apredictor is of the single shot isolation PVI success rate beforeablation, the predictor being a distributed initial temperature, andwherein the distributed initial temperature is approximately greaterthan about 31° C., and the single shot isolation PVI success rate is atleast approximately about 90%.

219. Use according to Clause 205, wherein the characteristic is apredictor is of the single shot isolation PVI success rate beforeablation, the predictor being a distributed initial temperature, andwherein the distributed initial temperature is approximately greaterthan about 30° C., and the single shot isolation PVI success rate is atleast approximately about 90%.

220. Use according to Clause 205, wherein the characteristic is apredictor is of the single shot isolation PVI success rate beforeablation, the predictor being a distributed initial temperature, andwherein the distributed initial temperature is approximately greaterthan about 29° C., and the single shot isolation PVI success rate is atleast approximately about 90%.

221. Use according to Clause 205, wherein the characteristic is apredictor is of the single shot isolation PVI success rate beforeablation, the predictor being a pre-ablation lowest temperature slope,and wherein the pre-ablation lowest temperature slope is approximatelygreater than about 0.75° C./sec, and the single shot isolation PVIsuccess rate is at least approximately about 90%.

222. Use according to Clause 205, wherein the characteristic is apredictor is of the single shot isolation PVI success rate beforeablation, the predictor being a pre-ablation lowest value temperature,and wherein the pre-ablation lowest value temperature is approximatelygreater than about 6° C., and the single shot isolation PVI success rateis at least approximately about 90%.

223. Use according to Clause 205, wherein the characteristic is apredictor is of the single shot isolation PVI success rate beforeablation, the predictor being a pre-ablation highest initialtemperature, and wherein the pre-ablation highest initial temperature isapproximately less than about 31° C., and the single shot isolation PVIsuccess rate is at least approximately about 90%.

224. Use according to Clause 205, wherein the characteristic is apredictor is of the single shot isolation PVI success rate beforeablation, the predictor being a pre-ablation initial temperaturevariation, and wherein the pre-ablation initial temperature variation isapproximately less than about 3° C., and the single shot isolation PVIsuccess rate is at least approximately about 95%.

225. Use according to Clause 205, wherein the characteristic is apredictor is of the single shot isolation PVI success rate beforeablation, the predictor being a pre-ablation initial impedancevariation, and wherein the pre-ablation initial impedance variationcomprises an optimal range of approximately less than about 20Ω, and thesingle shot isolation PVI success rate is at least approximately about88.5%.

226. Use according to Clause 205, wherein the characteristic is apredictor is of the single shot isolation PVI success rate beforeablation, the predictor being a pre-ablation lowest value impedancedrop, and wherein the pre-ablation lowest value impedance drop isapproximately greater than about 12Ω, and the single shot isolation PVIsuccess rate is at least approximately about 90%.

227. Use according to Clause 205, wherein the characteristic is apredictor is of the single shot isolation PVI success rate beforeablation, the predictor being a pre-ablation impedance drop variation,and wherein the pre-ablation impedance drop variation is approximatelygreater than about 20Ω, and the single shot isolation PVI success rateis at least approximately about 85%.

228. Use according to Clause 205, wherein the characteristic is apredictor is of the single shot isolation PVI success rate beforeablation, the predictor being a pre-ablation lowest value impedance droppercent, and wherein the pre-ablation lowest value impedance droppercent is greater than or equal to approximately about 12%, and thesingle shot isolation PVI success rate is at least approximately about90%.

229. Use according to Clause 205, wherein the characteristic is apredictor is of the single shot isolation PVI success rate beforeablation, the predictor being a pre-ablation impedance drop percentvariation, and wherein the pre-ablation impedance drop percent variationis less than about 20Ω, and the single shot isolation PVI success rateis at least approximately about 85%.

230. Use according to Clause 205, wherein when a number of electrodeswith initial impedance deviation from mean value is zero, the singleshot isolation PVI success rate is approximately about 92%.

231. Use according to Clause 205, wherein the characteristic is apredictor is of the single shot isolation PVI success rate beforeablation, the predictor being a difference of impedance between anteriorand posterior wall.

232. Use according to Clause 231, wherein the difference is less thanapproximately about 20Ω and the single-shot PVI success rate is at leastapproximately about 85% for the predetermined patient population.

233. Use according to Clause 231, wherein the difference is less thanapproximately about 20Ω and the single-shot PVI success rate is at leastapproximately about 85% for the predetermined patient population of atleast 25 patients.

234. Use according to Clause 231, wherein the difference isapproximately between 20 to 30Ω and the single-shot PVI success rate isat least approximately about 78% for the predetermined patientpopulation.

235. Use according to Clause 231, wherein the difference isapproximately between 20 to 30Ω and the single-shot PVI success rate isat least approximately about 78% for the predetermined patientpopulation of at least 75 patients.

236. Use according to Clause 231, wherein the difference isapproximately between 30 to 40Ω and the single-shot PVI success rate isat least approximately about 75% for the predetermined patientpopulation.

237. Use according to Clause 231, wherein the difference isapproximately between 30 to 40Ω and the single-shot PVI success rate isat least approximately about 75% for the predetermined patientpopulation of at least 60 patients.

238. Use according to Clause 231, wherein the difference isapproximately between 40 to 50Ω and the single-shot PVI success rate isat least approximately about 67% for the predetermined patientpopulation.

239. Use according to Clause 231, wherein the difference isapproximately between 40 to 50Ω and the single-shot PVI success rate isat least approximately about 67% for a predetermined patient populationof at least 34 patients.

240. Use according to Clause 231, wherein the difference isapproximately between 50 to 60Ω and the single-shot PVI success rate isat least approximately about 35% for the predetermined patientpopulation.

241. Use according to Clause 231, wherein the difference isapproximately between 50 to 60Ω and the single-shot PVI success rate isat least approximately about 35% for the predetermined patientpopulation of at least 11 patients.

242. Use according to Clause 231, wherein the difference is greater thanapproximately about 60Ω and the single-shot PVI success rate is at leastapproximately about 33% for the predetermined patient population.

243. Use according to Clause 231, wherein the difference is greater thanapproximately about 60Ω and the single-shot PVI success rate is at leastapproximately about 33% for the predetermined patient population of atleast 9 patients.

244. Use according to Clause 231, wherein the balloon catheter is afull-circle all electrode burning ablation catheter.

245. Use according to Clause 231, wherein the step of ablating tissue isfor a duration of 60 seconds.

246. Use according to Clause 205, wherein the characteristic is apredictor is of the single shot isolation PVI success rate beforeablation, and wherein pre-ablation mean initial impedance is thepredictor.

247. Use according to Clause 205, wherein the characteristic is apredictor is of the single shot isolation PVI success rate beforeablation, and wherein pre-ablation initial impedance variation is thepredictor.

248. Use according to Clause 205, wherein the characteristic is anevaluator of the single shot isolation PVI success rate post ablation,and wherein post-ablation lowest impedance drop is the evaluator.

249. Use according to Clause 205, wherein the characteristic is anevaluator of the single shot isolation PVI success rate post ablation,and wherein post-ablation impedance drop variation is the evaluator.

250. Use according to Clause 205, wherein the characteristic is apredictor is of the single shot isolation PVI success rate beforeablation, and wherein post-ablation mean temperature slope is theevaluator.

251. Use according to Clause 205, wherein the characteristic is anevaluator of the single shot isolation PVI success rate post ablation,and wherein post-ablation lowest temperature slope is the predictor.

252. Use according to Clause 205, wherein the characteristic is anevaluator of the single shot isolation PVI success rate post ablation,and wherein post-ablation mean temperature rise is the evaluator.

253. Use according to Clause 205, wherein the characteristic is anevaluator of the single shot isolation PVI success rate post ablation,and wherein post-ablation lowest temperature rise is the evaluator.

254. Use according to Clause 205, wherein the characteristic is anevaluator of the single shot isolation PVI success rate post ablation,and wherein post-ablation lowest impedance drop percentage is theevaluator.

255. Use according to Clause 205, wherein the characteristic is anevaluator of the single shot isolation PVI success rate post ablation,and wherein post-ablation variation of impedance drop percentage is theevaluator.

256. Use according to Clause 205, wherein the characteristic is apredictor is of the single shot isolation PVI success rate beforeablation, and wherein pre-ablation lowest impedance drop is thepredictor.

257. Use according to Clause 205, wherein the characteristic is apredictor is of the single shot isolation PVI success rate beforeablation, and wherein pre-ablation initial temperature variation is thepredictor.

258. Use according to Clause 205, wherein the characteristic is apredictor is of the single shot isolation PVI success rate beforeablation, and wherein pre-ablation maximum initial impedance is thepredictor.

259. Use according to Clause 205, wherein the characteristic is apredictor is of the single shot isolation PVI success rate beforeablation, and wherein pre-ablation mean initial anterior wall impedanceis the predictor.

260. Use according to Clause 205, wherein the characteristic is apredictor is of the single shot isolation PVI success rate beforeablation, and wherein pre-ablation lowest anterior wall impedance is thepredictor.

261. Use according to Clause 205, wherein the characteristic is apredictor is of the single shot isolation PVI success rate beforeablation, and wherein pre-ablation maximum anterior wall impedance isthe predictor.

262. Use according to Clause 205, wherein the characteristic is apredictor is of the single shot isolation PVI success rate beforeablation, and wherein pre-ablation anterior wall impedance variation isthe predictor.

263. Use according to Clause 205, wherein impedance values were amongthe electrodes of an anterior wall.

264. Use according to Clause 205, wherein the characteristic is apredictor is of the single shot isolation PVI success rate beforeablation, and wherein the predictor is determined by:

${Probability} \sim \frac{e^{Y}}{( {1 + e^{Y}} )}$Y ∼ 4.367 − 0.420 Δ T₀ − 0.0486 Δ Z₀

wherein ΔT₀ is initial impedance variation and ΔZ₀ is initialtemperature variation.

265. Use according to Clause 205, wherein the characteristic is apredictor is of the single shot isolation PVI success rate beforeablation, and wherein the predictor is determined by:

${Prob} \sim \frac{e^{Y}}{( {1 + e^{Y}} )}$Y ∼ 26.78 − 0.576 T_(0 max ) − 0.0632 Z_(0max )

wherein T_(0max) is highest initial temperature and Z_(0max) is highestinitial impedance.

266. Use according to Clause 205, wherein the characteristic is apredictor is of the single shot isolation PVI success rate beforeablation, and wherein the predictor is determined by:

${Prob} \sim \frac{e^{Y}}{( {1 + e^{Y}} )}$Y ∼ 27.70 − 0.540 T_(0 max ) − 0.0959 Z_(0max )

wherein T_(0max) is highest initial temperature and Z_(0max) is highestinitial impedance.

267. Use according to Clause 205, wherein the characteristic is apredictor is of the single shot isolation PVI success rate beforeablation, and wherein the predictor is determined by:

${Prob} \sim \frac{e^{Y}}{( {1 + e^{Y}} )}$Y ∼ 9.31 − 0.408 Δ T₀ − 0.0544 Z_(0max )

wherein ΔT₀ is initial temperature variation and Z_(0max) is highestinitial impedance.

268. Use according to Clause 205, the characteristic is a predictor isof the single shot isolation PVI success rate before ablation, andwherein the predictor is determined by:

${Prob} \sim \frac{e^{Y}}{( {1 + e^{Y}} )}$Y ∼ 22.61 − 0.622 T_(0 max ) − 0.0626 Δ Z₀

wherein T_(0max) is highest initial temperature and ΔZ₀ is initialimpedance variation.

269. Use according to Clause 205, wherein the characteristic is apredictor is of the single shot isolation PVI success rate beforeablation, and wherein the predictor is determined by:

${Prob} \sim \frac{e^{Y}}{( {1 + e^{Y}} )}$Y ∼ 11.53 − 0.439 Δ T₀ − 0.0856 Z_(0mean)

wherein ΔT₀ is initial temperature variation and Z_(0max) is meaninitial impedance.

270. Use according to Clause 205, wherein the characteristic is apredictor is of the single shot isolation PVI success rate beforeablation, and wherein the predictor is determined by:

${Prob} \sim \frac{e^{Y}}{( {1 + e^{Y}} )}$Y ∼ 26.52 + 0.013 Δ T₀ − 0.594 T_(0 max ) − 0.0122 Δ Z₀ − 0.0535 Z_(0max )

wherein ΔT₀ is initial temperature variation, T_(0max) is highestinitial temperature, ΔZ₀ is initial impedance variation, and Z_(0max) ishighest initial impedance.

271. Use according to any preceding clause, wherein the characteristicis an evaluator of the single shot isolation PVI success rate postablation, and wherein the evaluator is determined by:

${Prob} \sim \frac{e^{Y}}{( {1 + e^{Y}} )}$Y ∼ 1.562 + 0.2856 Δ T_(min) − 0.0629 Δ Z_(drop)

wherein ΔT_(min) is lowest temperature rise and ΔZ_(drop) is impedancedrop variation.

272. Use according to any preceding clause, wherein the characteristicis an evaluator of the single shot isolation PVI success rate postablation, and wherein the evaluator is determined by:

$P \sim \frac{e^{Y}}{( {1 + e^{Y}} )}$Y ∼ −0.507 + 0.206 Δ T_(min) + 0.083 Z_(dropmin)

wherein ΔT_(min) is lowest temperature rise and Z_(dropmin) is minimumimpedance drop.

273. Use according to any preceding clause, wherein the characteristicis an evaluator of the single shot isolation PVI success rate postablation, and wherein the evaluator is determined by:

$P \sim \frac{e^{Y}}{( {1 + e^{Y}} )}$Y ∼ 1.248 + 0.2486 Δ T_(min) − 0.0594 Δ Z_(drop) + 0.0419 Z_(dropmin)

wherein ΔT_(min) is lowest temperature rise and Z_(dropmin) is minimumimpedance drop.

274. Use according to any preceding clause, wherein the characteristicis an evaluator of the single shot isolation PVI success rate postablation, and wherein the evaluator is determined by:

$P \sim \frac{e^{Y}}{( {1 + e^{Y}} )}$Y ∼ 1.174 + 0.2515 Δ T_(min) − 0.0564 Δ Z_(drop)%

wherein ΔT_(min) is lowest temperature rise and Δ Z_(drop) is impedancedrop percent variation.

275. Use according to any preceding clause, wherein the characteristicis an evaluator of the single shot isolation PVI success rate postablation, and wherein the evaluator is determined by:

$P \sim \frac{e^{Y}}{( {1 + e^{Y}} )}$Y ∼ −0.644 + 0.170 Δ T_(min) + 0.107 Δ Z_(drop)%_(min)

wherein ΔT_(min) is lowest temperature rise and Z_(drop)%_(min) islowest impedance drop percent.

276. Use according to any preceding clause, wherein the characteristicis an evaluator of the single shot isolation PVI success rate postablation, and wherein the evaluator is determined by:

$P\text{∼}\frac{e^{Y}}{( {1 + e^{Y}} )}$Y∼0.339 + 0.187Δ T_(min) + 0.0737  Z_(drop)  %_(  min ) − 0.0368  Δ Z_(drop)%

wherein ΔT_(min) is lowest temperature rise, Z_(drop)%_(min) is lowestimpedance drop percent, and Δ Z_(drop)%) is impedance drop percentvariation.

277. Use according to any preceding clause, wherein the characteristicis an evaluator of the single shot isolation PVI success rate postablation, and wherein the evaluator is determined by:

$P\text{∼}\frac{e^{Y}}{( {1 + e^{Y}} )}$Y∼1.043 + 0.777 T_(min)^(′) + 0.171 Δ T_(min) + 0.0479 Z_(drop − min ) − 0.0589 Δ Z_(drop)

wherein T′_(min) is lowest temperature slope, ΔT_(min) is lowesttemperature rise, Z_(drop)-min is lowest impedance drop and ΔZ_(drop) isimpedance drop variation.

278. Use according to Clause 205, further comprising the step ofdisplaying a graphical representation of the independently controllableelectrodes and the ablation parameters.

279. Use according to Clause 278, wherein one ablation parametercomprises impedance measured proximate each electrode.

280. Use according to Clause 279, wherein the measured impedancecomprises impedance measured before ablation.

281. Use according to Clause 279, wherein the measured impedancecomprises impedance measured after ablation.

282. Use according to Clause 279, wherein the measured impedancecomprises impedance measured before and impedance measured afterablation.

283. Use according to Clause 278, wherein one ablation parametercomprises temperature measured proximate each electrode.

284. Use according to Clause 278, wherein one ablation parametercomprises a maximum temperature measured proximate each electrode duringthe ablating.

285. Use according to Clause 278, wherein one ablation parametercomprises a measured temperature rise from a beginning of ablating to anend of the ablating.

286. Use of an independently controlled multi-electrode radiofrequencyballoon catheter to treat a plurality of patients for paroxysmal atrialfibrillation, comprising the steps of:

delivering the radiofrequency balloon catheter having a plurality ofindependently controllable electrodes for radiofrequency ablation and amulti-electrode diagnostic catheter to one or more targeted pulmonaryveins;

ablating tissue of the one or more targeted pulmonary veins with one ormore of the plurality of the electrodes independently controlledmulti-electrode radiofrequency balloon catheter;

diagnosing the one or more targeted pulmonary veins using themulti-electrode diagnostic catheter; and

achieving at least one of a predetermined clinical effectiveness andacute effectiveness of the multi-electrode radiofrequency ballooncatheter and the multi-electrode diagnostic catheter in the isolation ofthe one or more targeted pulmonary veins, during and approximately 3months after the ablating step.

287. Use according to Clause 286, wherein acute effectiveness is definedby confirming if there is an entrance block in all targeted pulmonaryveins after adenosine and/or isoproterenol challenge.

288. Use according to Clause 287, further comprising: determining theacute effectiveness determined at approximately 3 months after theablating step; and

generating an estimated acute effectiveness at approximately 12 monthsafter the ablating step based on the acute effectiveness determined atapproximately 3 months.

289. Use according to Clause 288, wherein the estimated acuteeffectiveness at approximately 12 months is substantially similar to theacute effectiveness determined at approximately 3 months.

290. Use according to Clause 287, wherein the acute effectiveness isfurther defined by success greater than 90% for the plurality ofpatients.

291. Use according to Clause 287, wherein the acute effectiveness isfurther defined by success greater than 95% for the plurality ofpatients.

292. Use according to Clause 287, wherein a Type-1 error rate for powerthe acute effectiveness and the clinical effectiveness of all targetedveins are controlled at approximately a 5% level, the method or usefurther comprising:

determining whether the ablating is clinically successful for theplurality of patients if both the acute effectiveness and the clinicaleffectiveness indications are controlled at approximately the 5% level.

293. Use according to Clause 287, wherein the acute effectiveness is atleast 80% for the plurality of patients being at least 80 patients.

294. Use according to Clause 287, wherein the acute effectiveness is atleast 80% for the plurality of patients being at least 130 patients.

295. Use according to Clause 287, wherein the acute effectiveness is atleast 80% for the plurality of patients being at least 180 patients.

296. Use according to Clause 287, wherein the acute effectiveness is atleast 80% for the plurality of patients being at least 230 patients.

297. Use according to Clause 287, wherein the acute effectiveness isfurther defined by confirming if there is an entrance block in alltargeted pulmonary veins after adenosine and/or isoproterenol challengeusing a focal ablation catheter.

298. Use according to Clause 287, wherein the acute effectiveness isfurther defined by confirming if there is an entrance block in alltargeted pulmonary veins after adenosine and/or isoproterenol challengewithout using a focal ablation catheter.

299. Use according to Clause 286, wherein the ablating is administeredon the plurality of patients diagnosed with symptomatic paroxysmalatrial fibrillation.

300. Use according to Clause 286, wherein the step of diagnosing furthercomprises:

electrophysiological mapping of the heart.

301. Use according to Clause 286, wherein the multi-electrode diagnosticcatheter further comprises a high torque shaft with a halo-shaped tipsection containing a plurality of pairs of electrodes visible underfluoroscopy.

302. Use according to Clause 286, wherein the plurality of patients isat least 80.

303. Use according to Clause 286, wherein the plurality of patients isat least 130.

304. Use according to Clause 286, wherein the plurality of patients isat least 180.

305. Use according to Clause 286, wherein the plurality of patients isat least 230.

306. Use according to Clause 286, wherein the predetermined acuteeffectiveness is defined by ulceration being absent in the plurality ofpatients after the ablating.

307. Use according to Clause 286, wherein the predetermined acuteeffectiveness is defined by a complication rate of approximately 13% orfewer of the plurality of patients experiencing esophageal erythemaafter the ablating.

308. Use according to Clause 286, wherein the predetermined acuteeffectiveness is defined by a complication rate of approximately 25% orfewer of the plurality of patients experiencing new asymptomaticcerebral embolic lesions after the ablating.

309. Use according to Clause 286, wherein the predetermined acuteeffectiveness is defined by a complication rate of approximately 20% orfewer of the plurality of patients experiencing new asymptomaticcerebral embolic lesions after the ablating.

310. Use according to Clause 286, wherein the predetermined acuteeffectiveness is defined by a complication rate of approximately 5-9% orfewer of the plurality of patients experiencing a primary adverse eventby approximately 7 or more days after the ablating.

311. Use according to Clause 286, wherein inclusion criteria for theplurality of patients comprises:

a diagnosis with symptomatic paroxysmal atrial fibrillation; and

a patient capability to comply with uninterrupted per-protocolanticoagulation requirements.

312. Use according to Clause 286, wherein the predetermined acuteeffectiveness is defined by a total procedure time.

313. Use according to Clause 286, wherein the predetermined acuteeffectiveness is defined by a total ablation time.

314. Use according to Clause 286, wherein the predetermined acuteeffectiveness is defined by a total RF application time.

315. Use according to Clause 286, wherein the predetermined acuteeffectiveness is defined by a total dwell time of the multi-electroderadiofrequency balloon catheter.

316. Use according to Clause 286, wherein the predetermined acuteeffectiveness is defined by a total time to isolate all targetedpulmonary veins.

317. Use according to Clause 286, wherein the predetermined acuteeffectiveness is defined by a number and a total time of applications bythe multi-electrode radiofrequency balloon catheter per location of alltargeted pulmonary veins.

318. Use according to Clause 286, wherein the predetermined acuteeffectiveness is defined by a number and a total time of applications bythe multi-electrode radiofrequency balloon catheter per patient.

319. Use according to Clause 286, wherein the predetermined acuteeffectiveness is defined by a number and a total time of applications bythe multi-electrode radiofrequency balloon catheter per targeted vein.

320. Use according to any preceding clause, wherein the multi-electroderadiofrequency balloon catheter comprises:

a compliant balloon with a plurality of electrodes bonded configured todeliver RF energy to tissue of the pulmonary vein and sense temperatureat each electrode.

321. Use according to Clause 320, wherein clinical effectiveness isdefined by an incidence of early onset of one or more adverse eventswithin a predetermined time of the method or use being implemented.

322. Use according to Clause 321, wherein the predetermined time is atleast 7 days.

323. Use according to Clause 321, wherein the one or more adverse eventscomprise: death, atrio-esophageal fistula, myocardial infarction,cardiac tamponade/perforation, thromboembolism, stroke, TIA (TransientIschemic Attack), phrenic nerve paralysis, pulmonary vein stenosis, andthe major vascular access bleeding.

324. Use according to Clause 321, wherein the one or more adverse eventscomprise: incidence of individual adverse events from a primarycomposite; incidence of serious adverse device effect; incidence ofserious adverse events within 7 days, at least 730 days, and at least 30days following the ablating; incidence of non-serious adverse events;incidence of pre- and post-ablation asymptomatic and symptomaticcerebral emboli as determined by MRI evaluation; and frequency, anatomiclocation, and size (diameter and volume) of cerebral emboli by MRIevaluations at baseline, post-ablation and during follow-up.

325. Use according to Clause 321, wherein the one or more adverse eventsfor approximately 5-9% of the plurality of patients, the one or moreadverse events comprising:

NIHSS (National Institute of Health Stroke Scale) scores at baseline,post-ablation and during follow-up;

a summary of MoCA (Montreal Cognitive Assessment) and mRS (ModifiedRanking Scale) scores at baseline, 1 month and during further follow-up;a rate of hospitalization for cardiovascular events; a percentage (%) ofpulmonary vein isolation touch-up by focal catheter among the one ormore targeted veins;

a percentage (%) of subjects with use of focal catheter ablations fornon-PV triggers;

a percentage (%) of subjects with freedom from documented symptomaticatrial fibrillation (AF), atrial tachycardia (AT), or atypical (leftside) atrial flutter (AFL) episodes (episodes >30 seconds on arrhythmiamonitoring device from day 91 to 180);

a percentage (%) of subjects with freedom from documented atrialfibrillation (AF), atrial tachycardia (AT), or atypical (left side)atrial flutter (AFL);

one or more episodes that endure for 30 or more seconds on an arrhythmiamonitoring device from day 91 to 180 following the ablating; and

one or more procedural parameters including total procedure and ablationtime, balloon dwell time, RF application time, a number of RFapplications, fluoroscopy time and dose.

326. Use according to Clause 320, wherein the acute safety rate includescomplication rates of 10% or less and is defined by incidence ofasymptomatic cerebral embolic lesions at a discharge magnetic resonanceimaging (MRI).

327. Use according to Clause 320, wherein the acute effectiveness rateis 100% and is defined by electrically isolating all targeted pulmonaryveins without use of a focal ablation catheter.

328. Use according to Clause 320, wherein the acute effectiveness rateis defined by a freedom from documented atrial fibrillation, atrialtachycardia, or atypical atrial flutter episodes based onelectrocardiographic data through an effectiveness evaluation period (1year).

329. Use according to Clause 320, wherein the acute effectiveness rateis defined by pulmonary vein isolation touch-up by a focal catheteramong all targeted pulmonary veins.

330. Use according to Clause 320, wherein the predetermined clinicaleffectiveness rate is defined by 10% or less complication rates relatedto incidence of post-ablation symptomatic and asymptomatic cerebralemboli as compared to pre-ablation.

331. Use according to Clause 320, wherein the multi-electrode diagnosticcatheter is configured for electrophysiological recording andstimulation of the atrial region of the heart and is used in conjunctionwith the multi-electrode radiofrequency balloon catheter.

332. Use of an independently controlled multi-electrode radiofrequencyballoon catheter to treat a plurality of patients for paroxysmal atrialfibrillation, comprising:

delivering the radiofrequency balloon catheter having a plurality ofindependently controllable electrodes for radiofrequency ablation and amulti-electrode diagnostic catheter to one or more targeted pulmonaryveins; and

ablating tissue of one or more targeted pulmonary veins with one or moreof the plurality of the electrodes independently controlledmulti-electrode radiofrequency balloon catheter;

diagnosing all targeted pulmonary veins using the multi-electrodediagnostic catheter; and

achieving a predetermined rate of adverse events based on use of themulti-electrode radiofrequency balloon catheter and the multi-electrodediagnostic catheter in the isolation of all targeted pulmonary veins,during and approximately 6 months after the method or use.

333. Use of an independently controlled multi-electrode radiofrequencyballoon catheter to treat a plurality of patients for paroxysmal atrialfibrillation, comprising the steps of:

evaluating a number and size of all targeted pulmonary veins and anatomyof the left atrial;

puncturing the transseptal;

selectively positioning a multi-electrode esophageal temperaturemonitoring device in the vasculature with respect to all targetedpulmonary veins;

selectively positioning the radiofrequency balloon catheter in thevasculature with respect to all targeted pulmonary veins, themulti-electrode radiofrequency balloon catheter having a plurality ofindependently controllable electrodes for radiofrequency ablation;

selectively positioning a multi-electrode diagnostic catheter in thevasculature with respect to all targeted pulmonary veins;

ablating tissue of all targeted pulmonary veins with one or more of theplurality of the electrodes independently controlled multi-electroderadiofrequency balloon catheter;

confirming isolation of all targeted pulmonary veins using themulti-electrode diagnostic catheter;

confirming existence of an entrance block in all targeted pulmonaryveins; achieving a predetermined clinical effectiveness and/or acuteeffectiveness of the method or use, based on the confirmed existence ofthe entrance block, regarding the isolation of all targeted pulmonaryveins following the method or use.

334. Use according to any preceding clause, further comprising: mappingall targeted pulmonary veins using the diagnostic catheter.

335. Use according to any preceding clause, wherein exclusion criteriafor the plurality of patients comprises at least one of the following:

-   -   atrial fibrillation secondary to electrolyte imbalance, thyroid        disease, or reversible or non-cardiac cause;    -   previous surgical or catheter ablation for atrial fibrillation;    -   anticipated to receive ablation outside all targeted pulmonary        veins ostia and CTI region;    -   previously diagnosed with persistent, longstanding atrial        fibrillation and/or continuous atrial fibrillation >7 days,        or >48 hrs terminated by cardioversion;    -   any percutaneous coronary intervention (PCI) within the past 2        months;    -   valve repair or replacement and presence of a prosthetic valve;    -   any carotid stenting or endarterectomy;    -   coronary artery bypass grafting, cardiac surgery, valvular        cardiac surgical or percutaneous procedure within the past 6        months;    -   documented left atrium thrombus on baseline imaging;    -   LA antero posterior diameter greater than 50 mm;    -   any pulmonary vein with a diameter greater than or equal to 26        mm;    -   left ventricular ejection fraction less than 40%;    -   contraindication to anticoagulation;    -   history of blood clotting or bleeding abnormalities;    -   myocardial infarction within the past 2 months;    -   documented thromboembolic event within the past 12 months;    -   rheumatic heart disease;    -   awaiting cardiac transplantation or other cardiac surgery within        the next 12 months;    -   unstable angina;    -   acute illness or active systemic infection or sepsis;    -   diagnosed atrial myxoma or interatrial baffle or patch;    -   presence of implanted pacemaker, implantable cardioverter        defibrillator, tissue-embedded, or iron-containing metal        fragments;    -   significant pulmonary disease or any other disease or        malfunction of the lungs or respiratory system that produces        chronic symptoms;    -   significant congenital anomaly;    -   pregnancy or lactating;    -   enrollment in an investigational study evaluating another        device, biologic, or drug;    -   pulmonary vein stenosis;    -   presence of intramural thrombus, tumor or other abnormality that        precludes vascular access, or manipulation of the catheter;    -   presence of an IVC filter;    -   presence of a condition that precludes vascular access;    -   life expectancy or other disease processes likely to limit        survival to less than 12 months;    -   contraindication to use of contrast agents for MRI;    -   presence of iron-containing metal fragments in the patient; or    -   unresolved pre-existing neurological deficit.

336. Use according to any preceding clause, wherein the multi-electroderadiofrequency balloon catheter comprises:

a compliant balloon with a plurality of electrodes configured to deliverRF energy to tissue of all targeted pulmonary veins and sensetemperature at each electrode.

337. Use according to Clause 336, wherein the plurality of electrodes isoriented circularly to circumferentially contact with an ostia of thepulmonary vein.

338. Use according to Clause 336, further comprising using the pluralityof electrodes for visualization, stimulation, recording, and ablation.

339. Use according to Clause 336, wherein each electrode is configuredso an amount of power delivered to each electrode is controlledindependently.

340. Use according to Clause 336, wherein the multi-electroderadiofrequency balloon catheter further comprises a proximal handle, adistal tip, and a middle section disposed therebetween.

341. Use according to Clause 340, wherein the proximal handle is adeflection thumb knob allowing for unidirectional deflection, a balloonadvancement mechanism, and a luer fitting for balloon inflation andirrigation.

342. Use according to Clause 336, wherein the multi-electroderadiofrequency balloon catheter further comprises

a high-torque shaft configured to be rotated to facilitate accuratepositioning of the catheter tip to a desired; and

a unidirectional braided deflectable tip section.

343. Use according to any preceding clause, further comprising:

controlling irrigation to the multi-electrode radiofrequency ballooncatheter with an irrigation pump.

344. Use according to any preceding clause, further comprising:

administering uninterrupted anticoagulation therapy at least 1 monthprior to the procedure.

345. Use according to any preceding clause, wherein if the patient isreceiving warfarin/coumadin therapy, the patient must have aninternational normalized ratio (INR)≥2 for at least 3 weeks prior to theprocedure.

346. Use according to any preceding clause, wherein if the patient isreceiving warfarin/coumadin therapy, the patient must be confirmed tohave an international normalized ratio (INR)≥2 within 48 hourspre-procedure.

347. Use according to any preceding clause, further comprising:continuing anticoagulation therapy prior to the procedure.

348. Use according to any preceding clause, further comprising:

administering a transseptal puncture;

confirming an activated clotting time target of ≥350 sec. prior toinserting the multi-electrode radiofrequency balloon catheter into theleft atrium and maintaining throughout the procedure;

introducing the multi-electrode radiofrequency balloon catheter;

introducing of a multi-electrode circular diagnostic catheter;

ablating the pulmonary vein with the multi-electrode radiofrequencyballoon catheter;

determining in real time pulmonary vein isolation with themulti-electrode circular diagnostic catheter; and

confirming whether an entrance is blocked in the pulmonary vein.

349. Use according to any preceding clause, wherein the multi-electrodecircular diagnostic catheter comprises:

an elongated body having a longitudinal axis;

a distal assembly distal the elongated body, the distal assembly havinga helical form comprising a proximal loop and a distal loop, and ashape-memory support member extending through at least the proximalloop, the proximal loop and the distal loop being oriented obliquely atan angle relative to the longitudinal axis of the elongated body;

at least one irrigated ablation ring electrode mounted on the proximalloop;

a control handle proximal the elongated body; and

a contraction wire having a proximal end in the control handle and adistal end anchored in the proximal loop, the control handle including afirst control member configured to actuate the contraction wire tocontract the proximal loop,

wherein the proximal loop has a first flexibility and the distal loophas a second flexibility, and the second flexibility is greater than thefirst flexibility.

350. Use of an independently controlled multi-electrode radiofrequencyballoon catheter of treating a plurality of patients for paroxysmalatrial fibrillation by applying energy to tissue of a subject's heartproximate to an esophagus, phrenic nerve, or lung, comprising the stepsof:

achieving at least one of a predetermined clinical effectiveness andacute effectiveness of the procedure based on use of the radiofrequencyballoon catheter and a multi-electrode diagnostic catheter in theisolation of the one or more targeted pulmonary veins by:

positioning an expandable member proximate to the left atrium, theexpandable member of the multi-electrode radiofrequency balloon catheterhaving a longitudinal axis and including a plurality of electrodesdisposed about the longitudinal axis, each electrode capable of beingenergized independently, the plurality of electrodes including a firstelectrode having a first radiopaque marker and a second electrode havinga second radiopaque marker different from the first radiopaque marker;

viewing an image of the expandable member as well as the first andsecond radiopaque markers in the left atrium;

determining an orientation of the first and second radiopaque markerswith respect to a portion of the left atrium closest to the esophagus,phrenic nerve, or lung, of the subject;

moving one of the first and second radiopaque markers to a portion ofthe left atrium

closest to the esophagus, phrenic nerve or lung;

energizing one or more electrodes indexed to the one of the radiopaquemarkers proximate the portion close to the esophagus, phrenic nerve, orlung, at a lower energization setting as compared to other electrodes tocreate a transmural lesion in the left atrium with little or no effectto adjacent anatomical structures; and

electrophysiologically recording and stimulating the atrial region ofthe tissue proximate to the esophagus, phrenic nerve, or lung using themulti-electrode diagnostic catheter.

351. An ablation system for electrical signal isolation in portions oforgan tissues, the system comprising:

a power generator;

a catheter shaft extending along a longitudinal axis;

a plurality of electrodes disposed about the longitudinal axis to defineat least a circumferential surface about the longitudinal axis, eachelectrode independently connected to the power generator to provideelectrical energy to each independent electrode; and

a processor to control power delivery of the power generator to each ofthe independently controlled electrodes, the processor configured to:

-   -   (a) receive measurement signals representative of tissue        temperature and tissue impedance proximate each electrode in        contact with organ tissues and    -   (b) provide an indication for a probability of success in        isolating electrical signal propagation in a region of the organ        tissues in contact with the plurality of electrodes, the        probability of success being determined from the tissue        temperature values and tissue impedance values.

352. The system of clause 351, in which the temperature values areselected from one or more of (a) highest initial temperature; (b)variation in initial temperature; (c) lowest temperature rise; (d)lowest temperature slope; (e) mean temperature slope; (f) meantemperature rise; and

the impedance values are selected from one or more of:

-   -   (a) variation in initial impedance; (b) highest initial        impedance; (c) mean initial impedance; (d) initial impedance        deviation of all electrodes from mean value; (d) variation in        impedance drop; (e) lowest impedance drop; (f) lowest impedance        drop percent; (g) variation in impedance drop percent.

353. The system of clause 352, in which the indication of success isapproximately 90% when the initial impedance is less than about 20 ohms.

354. The system of clause 352, in which the indication of success isgreater than 90% when the highest initial impedance is less than about110Ω.

355. The system of clause 352, in which the indication of success isgreater than 90% when the mean initial impedance is less than about 95Ω356. The system of clause 352, in which the indication of success isgreater than 90% when the Highest Initial temp less than about 31degrees Celsius.

357. The system of clause 352, in which the indication of success isgreater than 90% when the Initial temp variation less than about 3°Celsius.

358. The system of clause 352, in which the indication of success isgreater than 90% when a number of electrodes with initial impedancedeviation from mean value is zero.

359. The system of clause 352, in which the indication of success isgreater than 85% Impedance drop Variation less than about 20Ω.

360. The system of clause 352, in which the indication of success isgreater than 90% when the Lowest Temp rise is equal to or greater thanabout 6° C.

361. The system of clause 352, in which the indication of success isgreater than 90% when the Lowest Impedance drop is equal to or greaterthan about 12Ω.

362. The system of clause 352, in which the indication of success isgreater than 90% when the Lowest Impedance drop Percent is equal to orgreater than about 12%.

363. The system of clause 352, in which the indication of success isgreater than 90% when the Lowest Temp slope is equal to or greater thanabout 0.75° C./sec.

364. The system of clause 352, in which the indication of success isgreater than 90% when the Mean Temp rise is equal to or greater thanabout 14° C.

365. The system of clause 351, in which the temperature values areselected from one or more of: (a) initial temperature variation ΔT₀; (b)highest initial temperature T_(0max); (c) lowest temperature riseΔT_(min); and

wherein the impedance values are selected from one or more of: (a)initial impedance variation ΔZ₀; (b) highest initial impedance Z_(0max);(c) mean initial impedance Z_(0mean); (d) impedance drop variationΔZ_(drop); (e) lowest impedance drop Z_(dropmin); (f) impedance droppercent variation Δ Z_(drop)%; (g) lowest impedance drop percentZ_(drop)%_(min).

366. The system of clause 365, wherein the probability of success isapproximately equal to

$\frac{e^{Y}}{( {1 + e^{Y}} )}$where Y˜4.167−0.220ΔT₀−0.0286ΔZ₀.

367. The system of Clause 365, wherein the probability of success isapproximately equal to

$\frac{e^{Y}}{( {1 + e^{Y}} )}$where Y˜9.11−0.208ΔT₀− 0.0524Z_(0max).

368. The system of Clause 365, wherein the probability of success isapproximately equal to

$\frac{e^{Y}}{( {1 + e^{Y}} )}$where Y˜11.53−0.219ΔT₀− 0.0856 Z_(0mean).

369. The system of Clause 365, wherein the probability of success isapproximately equal to

$\frac{e^{Y}}{( {1 + e^{Y}} )}$where Y˜2.61−0.62T_(0max)−0.066ΔZ₀.

370. The system of Clause 365, wherein the probability of success isapproximately equal to

$\frac{e^{Y}}{( {1 + e^{Y}} )}$where Y˜2.61-0.62T_(0max)−0.066ΔZ₀.

371. The system of Clause 365, wherein the probability of success isapproximately equal to

$\frac{e^{Y}}{( {1 + e^{Y}} )}$where Y˜6.78-0.576T_(0max)−0.0612Z_(0max).

372. The system of Clause 365, wherein the probability of success isapproximately equal to

$\frac{e^{Y}}{( {1 + e^{Y}} )}$where Y˜7.70-0.520T_(0max)−0.0959Z_(0mean).

373. The system of Clause 365, wherein the probability of success isapproximately equal to

$\frac{e^{Y}}{( {1 + e^{Y}} )}$where Y˜6.52+0.013ΔT₀− 0.594T_(0max)−0.012ΔZ₀−0.0315Z_(0max).

374. The system of Clause 365, wherein the probability of success isapproximately equal to

$\frac{e^{Y}}{( {1 + e^{Y}} )}$where Y˜1.562+0.856ΔT_(min)−0.069ΔZ_(drop).

375. The system of Clause 365, wherein the probability of success isapproximately equal to

$\frac{e^{Y}}{( {1 + e^{Y}} )}$and Y˜−0.307+0.206ΔT_(min)+0.083 Z_(dropmin)

376. The system of Clause 365, wherein the probability of success isapproximately equal to

$\frac{e^{Y}}{( {1 + e^{Y}} )}$and Y˜1.28+0.286ΔT_(min)−0.0594ΔZ_(drop)+0.0219 Z_(dropmin)

377. The system of Clause 365, wherein the probability of success isapproximately equal to

$\frac{e^{Y}}{( {1 + e^{Y}} )}$and Y˜1.174+0.315ΔT_(min)−0.0564 ΔZ_(drop)%

378. The system of Clause 365, wherein the probability of success isapproximately equal

$\frac{e^{Y}}{( {1 + e^{Y}} )}$and Y˜−0.624+0.170ΔT_(min)+0.107 Z_(drop)%_(min).

379. The system of Clause 365, wherein the probability of success isapproximately equal

$\frac{e^{Y}}{( {1 + e^{Y}} )}$and Y˜0.119+0.1867ΔT_(min)+0.0717 Z_(drop)%_(min)−0.0168 ΔZ_(drop)%.

380. The system of Clause 351 in which the probability of success isselected from one or more of clauses 352-379.

The method or uses, systems, and devices of this disclosure demonstratedhigh rates of substantial clinical effectiveness and safety in patientssuffering from PAF. The specific configurations, choice of materials andthe size and shape of various elements can be varied according to designspecifications or constraints requiring a system or method or useconstructed according to the principles of the disclosed technology.Such changes are intended to be embraced within the scope of thedisclosed technology. The presently disclosed embodiments, therefore,are considered in all respects to be illustrative and not restrictive.It will therefore be apparent from the foregoing that while particularforms of the disclosure have been illustrated and described, variousmodifications can be made without departing from the spirit and scope ofthe disclosure and all changes that come within the meaning and range ofequivalents thereof are intended to be embraced therein.

What is claimed is:
 1. A method to treat a predetermined patientpopulation for paroxysmal atrial fibrillation, the method comprising:ablating tissue of one or more targeted pulmonary veins with one or moreof a plurality of electrodes of a radiofrequency balloon catheter;determining a characteristic, based on ablation parameters of theradiofrequency balloon catheter, of single shot pulmonary vein isolation(PVI) success rate; and achieving, based on the characteristic and stepof ablating the tissue, a single shot isolation PVI success rate in anisolation of all targeted pulmonary veins for the predetermined patientpopulation.
 2. The method of claim 1, wherein the step of achieving thesingle shot isolation PVI success rate further comprises achieving atleast about a 91.7% success rate by ablating with a pre-ablation meaninitial impedance of less than about 95Ω.
 3. The method of claim 1,wherein the step of achieving the single shot isolation PVI success ratefurther comprises achieving at least about 88% success rate by ablatingwith a pre-ablation highest initial anterior wall impedance of about110Ω.
 4. The method of claim 1, wherein the step of achieving the singleshot isolation PVI success rate further comprises achieving at leastabout 87.5% success rate by ablating with a pre-ablation initialanterior wall impedance variation impedance range of less than about20Ω.
 5. The method of claim 1, wherein the characteristic is a predictorof the single shot isolation PVI success rate before ablation waslimiting a highest initial temperature to less than about 31° C. amongthe plurality of electrodes of the balloon catheter.
 6. The method ofclaim 1, wherein the step of achieving the single shot isolation PVIsuccess rate further comprises achieving at least about a 90% successrate by ablating with a mean initial impedance of less than about 95Ωfor and a highest initial impedance of less than about 110Ω.
 7. Themethod of claim 1, wherein the characteristic is a predictor of thesingle shot isolation PVI success rate before ablation, the predictorbeing mean initial temperature, and wherein the mean initial temperatureis approximately less than about 28° C. and the single shot isolationPVI success rate is at least approximately about 90%.
 8. The method ofclaim 1, wherein the characteristic is a predictor of the single shotisolation PVI success rate before ablation, the predictor being apre-ablation lowest temperature slope, and wherein the pre-ablationlowest temperature slope is approximately greater than about 0.75°C./sec, and the single shot isolation PVI success rate is at leastapproximately about 90%.
 9. The method of claim 1, wherein thecharacteristic is a predictor of the single shot isolation PVI successrate before ablation, the predictor being a pre-ablation lowest valuetemperature, and wherein the pre-ablation lowest value temperature isapproximately greater than about 6° C., and the single shot isolationPVI success rate is at least approximately about 90%.
 10. The method ofclaim 1, wherein the characteristic is a predictor of the single shotisolation PVI success rate before ablation, the predictor being apre-ablation initial impedance variation, and wherein the pre-ablationinitial impedance variation comprises an optimal range of approximatelyless than about 20Ω, and the single shot isolation PVI success rate isat least approximately about 88.5%.
 11. The method of claim 1, whereinwhen one or more of the plurality of electrodes with initial impedancedeviation from mean value is zero, the single shot isolation PVI successrate is approximately about 92%.